factors of adherence to treatment with trospium in employees

Urological Science xxx (2017) 1e8 Contents lists available at ScienceDirect Urological Science journal homepage: www.urol-sci.com Original article Factors of adherence to treatment with trospium in employees Kirill Vladimirovich Kosilov a, b, *, Sergay Alexandrovich Loparev c, Irina Gennadyevna Kuzina a, Olga Viktorovna Shakirova b, Natalia Sergeevna Zhuravskaya b, Alexandra Lobodenko d a Department of Social Sciences, School of Humanities, Far Eastern Federal University, Vladivostok, Primorsky region, Russian Federation Department of Theory and Methods of adaptive physical education, Far Eastern Federal University, Vladivostok, Primorsky region, Russian Federation c Department of Urology, City polyclinic No 3, Vladivostok, Russian Federation d Institute of Humanities, Far Eastern Federal University, Vladivostok, Primorsky region, Russian Federation b a r t i c l e i n f o a b s t r a c t Article history: Received June 2016 Received in revised form 25 September 2016 Accepted January 2017 Available online xxx Aim: To conduct a comprehensive study of adverse factors and decreasing patients’ adherence during treatment with trospium Materials and methods: During 12 months, 977 patients receiving trospium were studied regarding demographic, socioeconomic, and medical parameters by studying employer’s records, extracts from income tax returns, questionnaires OABq-SF, MOS SF-36, ICIQ-SF, and questionnaires concerning demographic and social status, voiding diaries, and uroflowmetry Results: In total, 54.4% and 35.5% of patients preserved adherence to treatment with trospium during months and 12 months, respectively The average time of reaching a 30-day break in trospium administration was 182 days Patients diagnosed with urge urinary incontinence and overactive bladder OAB (56.1%; 40.7%), having severe incontinence symptoms (56.1%), showing objectively high treatment efficacy (25.3%), and individuals subjectively satisfied with treatment outcome (57.5%) prevail among adherent patients, a significant minority is heavy coffee drinkers (14.5%) Individuals who are healthcare and education employees having annual and monthly income significantly higher than the mean income of patients receiving trospium also prevail among adherent patients (25.0%; 32.5%) Adherent patients are significantly older (56.3) than patients less adherent to the treatment Conclusion: This experiment allowed for the first time the determination of the complexity of heterogeneous medical, socioeconomic, and demographic factors affecting patients’ adherence in treatment with trospium Copyright © 2017, Taiwan Urological Association Published by Elsevier Taiwan LLC This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/) Keywords: adherence of treatment employees incontinence lower urinary tract symptoms trospium Introduction The prevalence rates of lower urinary tract symptoms (LUTS) and, particularly, overactive bladder (OAB) symptoms remain consistently high worldwide.1,2 The prevalence of ОАВ is significantly higher in the elderly and women.3 The mean incidence of ОАВ symptoms “at least sometimes” for all races is 26e33% in men and 27e46% in women.4 Furthermore, 8% of men and 20% of women at the age of 18e70 years reported to have OAB symptoms “frequently”.5,6 * Corresponding author Ayax 10, F733, DVFU, Vladivostok, RUVVO, Russian Federation E-mail address: oton2000@mail.ru (K.V Kosilov) LUTS are often accompanied with depression, anxiety, decreased mental and physical activity, social isolation, and sexual health problems.7,8 Apart from its negative effect on health-related quality of life in many men and women, direct costs for LUTS treatment are very high; in 2009, they amounted to $ 22.3 billion only in the USA The presence of LUTS causes substantial losses for the employer and the employee and decreased work productivity, as observed in individuals suffering from asthma or chronic arthritis.9e11 Efficacy and safety of the available range of antimuscarinic drugs (AM) is generally recognized at the moment.12 Additionally, new advanced drugs appear having the mechanism of therapeutic effect associated with affecting b3-adrenoceptors Nevertheless, LUTS management continues to be a challenge currently One of the reasons include poor adherence of patients to treatment with AM drugs.13,14 http://dx.doi.org/10.1016/j.urols.2017.01.001 1879-5226/Copyright © 2017, Taiwan Urological Association Published by Elsevier Taiwan LLC This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/) Please cite this article in press as: Kosilov KV, et al., Factors of adherence to treatment with trospium in employees, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.01.001 K.V Kosilov et al / Urological Science xxx (2017) 1e8 In previous researches, we drew our attention to the patient's poor adherence to AM drugs treatment,15e17 which is consistent with the other authors' data.18 Poor adherence to physician’s prescriptions may be determined by medical, social, economic, demographic, psychological, and other factors.19,20 We have established correlation between adherence to prescriptions and efficacy of AMs, development of side effects, a regimen and a method of АМ administration, and pharmacology of different drugs Sometimes the results of the studies differ significantly among different authors For example, in one of the studies, it was found that adherence to treatment with fesoterodine is significantly higher than that with solifenacine and lolnerodinum.21 In other studies, conclusions were not so unambiguous.22,23 It was found that adherence to treatment with AM drugs is significantly affected by the cost of the drug, a possibility to get insurance treatment, and the number of days of disability leave.24 However, we failed to find studies in the available literature regarding correlation between adherence to treatment with a certain АМ drug and a wide range of medical, pharmacodynamic, socioeconomic, and demographic factors that could affect the patient’s choice We were also unable to determine information regarding comparison of significance of such factors in the making of a patient’s behavioral decision In our earlier works, we studied the effect of combination of some АМ drugs, particularly trospium, of decreased and increased dosage, on the activity of ОАВ symptoms Trospium chloride is a quaternary ammonium compound, which does not affect the central nervous system and causes no side effects, associated with influence on the central nervous system.25 We have suggested that studying a wide range of factors, affecting adherence to treatment with trospium, could help to identify the most significant of them Probably, the understanding of significance level of different factors and possibility to affect some of them would help to improve the adherence and manageability of treatment process Therefore, the purpose of this study was to study the significance of the factors affecting adherence to treatment with trospium in the cohort of employees to increase the efficacy of management of various LUTS forms Methods 2.1 Background information about the experiment The study design is presented in Figure The study was conducted at the premises of the Regional Diagnostics Center of the City Polyclinic No of Vladivostok from June 1, 2013 until February 5, 2015 It was a randomized, blinded prospective experiment regarding the factors affecting patients’ adherence to treatment with trospium According to the experiment protocol, among all the patients aged 18e60 years who visited the above institutions concerning LUTS, we selected patients admitted on the oddnumbered days of the month and prescribed with a long-term (> year) treatment with trospium only.25 Selection of patients into groups with various forms of LUTS was performed using stratified randomization ensuring equal gender representation The selection scheme is presented in Figure Electronic patient records and their test results were anonymized (they were assigned with numbers) to blind the members of the study group performing analysis of the results To calculate the sample size, we considered the confidence level of 95% and a confidence interval of ±5% 2.2 Inclusion/exclusion criteria and factors studied Patients with the following diagnoses were included in the groups for participation in the experiment: overactive bladder, OAB (ICD-9-CM: 596.51 converts directly to 2015 ICD-10-CM N32.81); urge incontinence, UUI (ICD-9-CM: 788.31 converts directly to 2015 ICD-10-CM N39.41); mixed incontinence, MI (ICD-9-CM: 788.33 converts directly to 2015 ICD-10-CM N39.46); and nocturia (ICD-9CM: 788.43 converts directly to 2015 ICD-10-CM R35.1).26 The diagnosis was confirmed by the data from voiding diaries, questionnaires OAB questionnaire short form (OABq-SF), and results of uroflowmetry.27 Furthermore, the criteria for inclusion in the group were employment for at least months before the start of the experiment and availability of the policy of obligatory medical insurance The exclusion criteria were terminal cancer, administration of AMs within months before the start of the experiment, and unemployment During the active phase of the experiment (12 months), all the patients were administered with trospium chloride as monotherapy 15 mg twice a day after meal, as prescribed by the urologist Every day during the year, the patients completed voiding diaries In these diaries they noted data regarding the amount, volume, time, and specific characteristics of urination, urgency episodes, incontinence, side effects, and time of trospium intake The diaries were also supplemented with a column wherein the patients included information about smoking and consumption of caffeinated food and drinks as well as alcohol Before the study, after the 6th month (1st checkpoint) and in the end of the follow-up period (2nd checkpoint), all patients underwent the following diagnostic procedures: (1) uroflowmetry, evaluation of urodynamics during the evacuation phase with calculation of urine volume (mL), average urine flow rate (Qaver, mL/ s), maximum urine flow rate (Qmax, mL/s), which provides objective evaluation of urination disorders; (2) completion of the questionnaire OABq-SF to specify the form and severity of urination disorders; a score of > was considered as urination disorder of the certain type; (3) completion of the questionnaire “The Medical Outcomes Study 36-Item Short-Form Health Survey” (MOS SF-36) to determine the general effect of health on the quality of life The questionnaire MOS SF-36 consists of eight items, each characterizing a certain aspect of quality of life: physical functioning (PF), role-physical (RР), bodily pain (ВP), general health (GH), vitality (VT), social functioning (SF), role-emotional (RE), and mental health (MH) The scale ranges from to 100;28 (4) completion of the questionnaire “International Consultation on Incontinence Questionnaire-Short Form” (ICIQ-SF), a specialized tool helping to determine the effect of urinary incontinence (UI) on the quality of life (maximum score is 21);29 (5) completion of free-form questionnaires, containing information about main descriptive demographic and social characteristics of patients; and (6) studying of employer’s records (an extract from the employment agreement), statement of income from the tax inspectorate Medical factors under study included a form of urination disorder, severity of UI symptoms, presence of side effects due to trospium administration, treatment efficacy, treatment satisfaction, experience of treatment with any other AMs, awareness of methods of LUTS treatment, comorbid conditions (Charlson Comorbidity Index), administration of drugs concerning other diseases, bad habits, and sleepewake cycle disturbances.30 Additionally, we studied the characteristics of the urination disorder The degree of UI was defined as severe when more than three episodes were observed during the day Defining caffeine abuse, we assumed that the highest daily dose of caffeine recommended by the manufacturers does not exceed 300 mg.31 Smoking of more than five cigarettes a day was defined as tobacco abuse, and the score > on the AUDIT scale was defined as alcohol abuse.32,33 Socioeconomic factors under study included annual salary and average monthly salary; number of individuals with the level of income lower than the living minimum wage; number of sick leave Please cite this article in press as: Kosilov KV, et al., Factors of adherence to treatment with trospium in employees, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.01.001 K.V Kosilov et al / Urological Science xxx (2017) 1e8 10 1250 The percentage of the cost of trospium from salary 1193.5 1150 1068.6 1050 950 Monthly salary 959.1 850 855.3 750 748.6 659.7 650 705.6 598.5 550 499.3534.8 9.2 8.4 7.7 7.1 6.3 5.9 5.2 5.1 4.8 4.5 450 10 20 30 40 50 60 70 80 10 90 20 30 40 50 60 70 80 90 Proportion of day covered (%) Proportion of day covered (%) Figure (A) Dependence between shares of days of trospium treatment and monthly payment (B) Share of trospium cost in employee’s salary Black unmarked line indicates the trend with linear filtering (n ¼ 977) 98.3 98.1 T h e p e r c e n t ag e o f p a t i e n t s a d h e r e n t t o t r o s p i u m 100 90 96.5 93.1 94.2 86.1 82.3 81.5 80 78 70 73.4 76.9 71.5 67.5 65.2 64.7 60.6 63.1 60.7 59.1 60 57.2 60.7 56.1 56.1 53 50 56.1 47 48.2 44 46.7 42.1 38.5 40 40.7 42.6 30.4 30 Urge incontinence (n=173) 20 10 26.1 26.5 23.1 22.6 Overactive bladder (n=572) 19.6 16.5 16.2 13.9 9.4 Mixed incontinence (n=117) 11.3 12.8 8.7 7.7 4.3 Nocturnal incontinence (n=115) start 10 11 12 months Figure Compliance with trospium treatment depending on different forms of lower urinary tract symptoms (n ¼ 977) days and their cost for the employer; number of sick leave days and employer’s expenses for the sick leave certificate; number of full- and part-time employees; monthly expenses for trospium and other drugs, square of these expenses, percentage of these expenses in overall patients’ expenses, and their square; and employee turnover, a percentage of employees having changed the place of employment within years before the experiment, and time of work at one place The level of salary and expenses presented are adjusted for inflation to the price of the US dollar as of June 2012 Please cite this article in press as: Kosilov KV, et al., Factors of adherence to treatment with trospium in employees, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.01.001 K.V Kosilov et al / Urological Science xxx (2017) 1e8 2.3 Evaluation of adherence and non-adherence Patients’ adherence to treatment was calculated as the time from the start of the experiment until the 30-day break in trospium administration Adherence was calculated separately for each potential affecting factor The average level of patient’s adherence was defined as the percentage of days during the year from the beginning of solifenacin administration during which he took the drug according to the prescription All patients were divided into three cohorts to compare the significance of factors affecting adherence: adherent employees (adherence  80%), poorly adherent (< 80%, but  50%) and non-adherent (< 50%) 2.4 Statistical analysis Analysis of time of feature survival (adherence) by the threeparameter Weibull distribution was performed using the model of waiting for a 30-day break in trospium administration For the employees included in the study cohort, we used the models of preserving of adherence with double right type censoring Goodness of fit of the Weibull distribution to data was evaluated using the HollandereProschan test Modeling of influence with a gamma distribution and a log link function was used for the evaluation of medical, social, and economic factors, including the diagnosis form, severity of symptoms and side effects, objective and subjective treatment outcome, presence of bad habits, comorbidity, experience of use of АМ drugs, age, and professional occupation These models were also used for controlling monthly and annual salary, their square, the percentage of expenses for trospium and other drugs, their square, number of sick leave days and their cost, and its square as well Significance of difference of parameters between groups was also controlled by regression models In some cases, the calculation of the Spearman rank correlation coefficient was used for the determination of relationship between the processes of parameter changes For the employees with different adherence levels (higher and lower than 80%, lower than 50%) modeling of significance level for the effect of different factors was performed separately The differences were considered significant if p < 0.05; all p values are two-sided All statistical analyses were performed using SAS version 8.0.2 (SAS Institute Inc., Cary, NC) 2.5 Ethical principles The principles of the Declaration of Helsinki were the priority in development of the design and conducting of the experiment All the patients of the experiment signed the informed consent prior to the experiment The study design was approved by the local Ethics Committee Results In total, the proportion of patients who were able to preserve adherence to treatment were 70.6% during the first months (1st checkpoint), 54.4% during months, and 35.5% at the end of the experiment (2nd checkpoint) The mean time of reaching a 30-day break in trospium administration was 182 days Table provides some demographic, social, and economic characteristics of patients in the experiment, with different levels of adherence to treatment The mean age of the most adherent patients [56.3 (5.9)] proved to be higher than the age of the patients with moderate and low level of adherence to treatment with trospium ( 0.05;  0.05) The percentage of healthcare or education employees was higher in the group with high treatment adherence (p  0.05; p  0.01) The percentage of retail employees was significantly lower in this group than in the group with moderate (p  0.05) and low (p  0.01) adherence levels Mean values of annual salary and monthly salary in the group with adherence level of  80% were significantly higher than that in the group with moderate (p  0.05) and low (p  0.01) adherence levels The percentage of monthly expenses for trospium in the group with high adherence was lower than that in the non-adherent group Figure demonstrates increased patients’ adherence upon increase of their monthly salary and decrease of the percentage of expenses for trospium Analyzing the regression model of salaryadherence correlation, we found that the influence of annual salary and its square on patients’ adherence was direct and significant (p  0.05; p  0.05) Evaluation of the effect of monthly salary share and the square of the percentage of expenses for trospium using the regression model allowed to establish that the possibility of such effect is significant (p  0.05; p  0.05) Regressions of the effect of age and professional occupation also showed acceptable confidence level (p  0.05; p  0.01) Regression models of other non-medical factors under study established statistical homogeneity in the cohorts At the first checkpoint, the score for RP, GH, SF, RE, and MN parameters was significantly lower in non-adherent patients than in groups with high and moderate adherence level At the second checkpoint, the score for PF, RP, GN, SF, RE and MN parameters was significantly higher in the group of adherent patients than in other two groups Table shows medical characteristics and health-related factors in patients with different levels of adherence to treatment with trospium The percentage of adherent patients among patients diagnosed with UUI was significantly higher (56.1%) than patients with moderate (31.2%) and low (12.1%) adherence (p  0.01; p  0.01, respectively) The percentage of patients with high and moderate adherence diagnosed with OAB (40.7% and 51.9%, respectively) was significantly higher (p  0.01; p  0.01) than that of non-adherent patients with the same diagnosis (7.3%) The percentage of adherent patients (56.1%) with severe incontinence (episode of UI  3/day) was significantly higher than that of patients with moderate adherence level (31.2%; p  0.01) and nonadherent patients (12.2%; p  0.01) The percentage of patients with satisfactory efficacy of treatment among adherent patients was significantly higher than that of patients with moderate (p  0.05) and low (p  0.01) adherence level The number of adherent patients abusing caffeine was significantly lower than that of other groups (p  0.01; p  0.01) Values of the Charlson Comorbidity Index were statistically homogeneous in all groups Regression models of influence of the diagnosis, severity of symptoms, treatment efficacy, and treatment satisfaction were calculated for the groups of patients with poor, moderate, and high adherence Analyzing each adherence level, we compared the results to each other It was found that the above factors have a significant effect on the level of adherence to treatment with trospium among employees (p  0.01) After analyzing the results of OABq-SF, we found that the values of UUI of 1.1 (0.9) and night urination of 0.8 (0.7) in adherent patients at the second checkpoint were significantly lower than those in other groups of adherence (p  0.05; p  0.05) Mean scores for self-assessment of urination-related quality of life on the ICIQ-SF scale in patients with high adherence after the end of the experiment were significantly higher (lower scores) than in other groups (p  0.05; p  0.05) Analysis of the results of urodynamics evaluation with voiding diaries showed almost similar results According to uroflowmetry data, in the group of adherent patients, bladder Please cite this article in press as: Kosilov KV, et al., Factors of adherence to treatment with trospium in employees, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.01.001 K.V Kosilov et al / Urological Science xxx (2017) 1e8 Table Demographic, social, and economic properties of employed patients who were receiving trospium (n ¼ 977) Level of adherence Adherence  50%, < 80% (n ¼ 430) Adherence < 50% (n ¼ 203) Adherence  80% (n ¼ 344) p Parameters Mean (SD) Mean (SD) Mean (SD) p1/2 p2/3 p1/3 Age Number of children Annual salary1 Average salary monthly1 Days of disability Disability cost Sick leave cost Sick leave days Monthly expenses on trospium Monthly expenses on other drugs Tenure (years with employers) 40.2 0.9 $8,102 $675 6.9 415 178 7.9 $27.4 $49.8 15.7 7.6 0.3 $1,178 $98.5 1.8 49 37 2.7 4.0 7.4 8.7 43.3 1.1 $11,378 $948 9.0 491 288 11.5 $27.4 $69.5 12.1 7.0 0.3 $2,491 $207.5 2.4 79 39 4.1 2.9 7.3 8.1 56.3 1.1 $18,117 $1,509 8.1 211 348 10.9 $27.4 $195.7 11.9 5.9 0.5 $2,993 $249.6 3.1 26 26 5.6 1.8 13.0 10.7 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.01 0.05 0.05 0.05 0.01 0.01 0.05 0.05 0.05 0.05 0.05 0.01 0.05 Parameters Number % Number % Number % p1/2 p2/3 p1/3 Female Married Not married Field of activity: Industry Transportation Retail Agriculture Education Medicine Other Persons with low income Persons with full-time working day Persons with combining work Employee turnover2 117 132 71 57.6 65.0 35.0 244 346 84 56.7 80.4 19.5 208 223 121 60.5 64.8 35.2 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 17 34 56 39 11 17 29 10 189 79 31 8.4 16.7 27.6 19.2 5.4 8.4 14.3 4.9 93.1 38.9 15.3 59 67 74 39 87 76 28 21 412 156 48 13.7 15.6 17.2 9.1 20.2 17.7 6.5 4.9 95.8 36.3 11.2 35 32 27 41 86 112 11 326 151 59 10.2 9.3 7.8 11.9 25.0 32.5 3.2 1.2 94.8 43.9 17.1 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.05 0.01 0.05 0.01 0.01 0.05 0.05 0.05 0.05 0.05 Remark SD ¼ standard deviation A sum of employees with adherence < 50%, 10 employees with adherence 50%, but < 80%, and employees with adherence  80% had missing salary information Specified number of workers changed jobs in the last years Table Medical characteristics and parameters related to the health of patients who were receiving trospium (n ¼ 977) Level of adherence Adherence  80% (n ¼ 344) Adherence 50%, < 80% (n ¼ 430) Adherence < 50% (n ¼ 203) p Parameters N % N % N % p1/2 p2/3 p1/3 Urge UI Mixed UI Nocturnal UI OAB Severe symptoms (EUI  3/day) Efficacy of treatment (1 CP) Efficacy of treatment (2 CP)1 Satisfaction with treatment (1 CP) Satisfaction with treatment (2 CP)2 Unsatisfactory experience in treating other AM Awareness of treatment options of OAB and UI Taking medications to treat comorbidities Bad habits: alcohol abuse smoking caffeine abuse Observance of sleep-wake cycle 21 78 62 42 51 84 21 68 17 159 167 117 12.1 66.6 53.9 7.3 12.2 41.4 10.3 33.3 8.4 78.3 82.2 57.6 55 30 48 297 132 217 126 196 129 374 389 261 31.2 25.6 41.7 51.9 31.6 50.5 18.2 45.6 30.0 86.9 90.5 60.7 97 233 234 231 197 268 198 296 291 245 56.1 7.7 4.3 40.7 56.1 67.1 25.3 77.9 57.5 86.0 84.6 71.2 0.05 0.01 0.05 0.05 0.05 0.05 0.05 0.05 0.01 0.05 0.05 0.05 0.01 0.01 0.01 0.01 0.01 0.05 0.05 0.05 0.01 0.05 0.05 0.05 0.01 0.01 0.01 0.01 0.01 0.01 0.05 0.01 0.01 0.05 0.05 0.05 11 102 67 159 5.4 50.2 33.0 78.3 24 221 127 304 5.6 51.4 29.5 70.7 32 149 50 278 9.3 43.3 14.5 80.8 0.05 0.05 0.05 0.05 0.05 0.05 0.01 0.05 0.05 0.05 0.01 0.05 AM ¼ antimuscarinic agents; CP ¼ check point; EUI e episodes of urge incontinence; N ¼ number; OAB ¼ overactive bladder; SD ¼ standard deviation; UUI ¼ urge urinary incontinence Total percentage of urge, mixed, nocturnal incontinence and OAB в сумме exceeds 100% due to the fact that the combination of these diseases may occur in one person Efficacy of treatment, shows the number of patients with the score  according to OABq-SF and normal uroflowmetry results after the 6th month (1 checkpoint; N ¼ 532) and 12th month (2 checkpoint; N ¼ 344) of observation Satisfaction with treatment, shows the number of patients with normal scores according to ICIQ-SF and MOS SF-36 after the 6th month (1 checkpoint) and 12th month (2 checkpoint) of observation Please cite this article in press as: Kosilov KV, et al., Factors of adherence to treatment with trospium in employees, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.01.001 K.V Kosilov et al / Urological Science xxx (2017) 1e8 volume and maximum urine flow rate characterizing accumulative and evacuation functions have changed significantly The percentage of patients with < 80% adherence, in which episodes of nocturnal incontinence (NI) and MI were observed, was 21.8%, while the percentage of patients with  80% adherence proved to be 1.4% At the same time, 7.8% of poorly adherent patients and 9.9% of patients highly adherent to the physician’s orders were found among the patients with UUI Figure demonstrates a change of the percentage of patients adherent to treatment, depending on the LUTS form for the whole follow-up period Patients with UI were the most adherent to treatment (56.1%) No significant differences between the percentage of adherent patients with UI and OAB were found The correlation coefficient for these curves was r ¼ 0.86 (p  0.01) The correlation coefficient between the curves, representing the change in the percentage of adherent patients with MI and NI was r ¼ 0.93 (p  0.01) After the 2nd month of follow-up, the percentage of patients with UI adherent to the treatment was significantly higher than that of adherent patients with MI and NI (p  0.01) Significant differences between the percentage of adherent patients with OAB on the one hand and MI and NI on the other hand appeared after the 5th month of the experiment The level of adherence to treatment is significantly higher in patients with UUI  3/day after the 3rd month of follow-up (p  0.05) The percentage of patients with UUI  decreased smoothly during the whole follow-up period, while the percentage of patients with moderate symptoms decreased dramatically from the 2nd to 4-5th months The curves, describing the change of the percentage of adherent patients, demonstrate the level of direct correlation r ¼ 0.6 (p  0.05) The number of patients (43%) who indicated medical factors (more than 80% of them were side effects and lack of the result) were the highest Economic factors were crucial for 33% of patients (more than 80% of them was the high cost of trospium and high cumulative cost of purchased drugs) The percentage of psychological factors was 15% (more than a half of them were negative experience of treatment with AMs) Also, 9% of patients stated social factors as a reason for refusal or long-term break in treatment Dry mouth was the main reason for refusal or long-term break in treatment in 6.3% of patients (the highest percentage was in the group of patients with poor treatment adherence, 29.1%) The significant percentage (5.1%) of refusals associated with side effects was due to rash, itching, and xeroderma (the highest percentage was also in the group of non-adherent patients, 7.9%) The percentage of patients who refused treatment because of these symptoms differed significantly in the groups with different adherence levels (p  0.05) Discussion This experiment showed that parameters such as elderly age, belonging to the groups of education, and healthcare or retail employees are the factors affecting patients’ adherence in following physician prescriptions Patients’ adherence directly depends on the size of their monthly salary and its percentage that is spent for buying trospium A high level of salary and the small percentage of expenses for trospium significantly increase patients’ adherence We found that at the second checkpoint, patients with high adherence assessed efficacy of PF, RP, RE, SF, VT, MH, and GH significantly higher too Self-assessment of quality of life related to urination disorders in adherent patients at the end of the experiment was also significantly higher than that in other groups Studying medical factors influencing the adherence, we established that among the most adherent patients having followed all prescriptions, the percentage of patients diagnosed with UUI (56.1%) and OAB (40.7%), severe incontinence (65.5%), and with treatment efficacy confirmed by special questionnaires and instrumental methods was significantly higher According to the study, patients with NI and MI show poorer adherence to physician’s orders than those who have UUI observed This fact is in conflict with data on high efficacy of trospium in all forms of UI.12,14,25 However, there is a very high percentage of patients having severe symptoms (more than episodes/day) among patients with UUI In turn, patients with severe UI symptoms are the most adherent to drug administration Only 6.5% of individuals with NI and MI were found among the patients having severe UI symptoms, while others were diagnosed with UUI Thus, the majority of patients with NI and MI had relatively a small number of incontinence episodes, which, in our opinion, could affect their behavior and did not contribute to high adherence to physician’s orders Urodynamic state of the lower urinary tract according to the data of uroflowmetry, voiding diaries, and OABq-SF changed the most significantly in majority of parameters (8 of 11) in the cohort of patients who were most adherent to treatment It was found that the current treatment outcome affects patients’ adherence directly The percentage of patients adherent to treatment but not satisfied with its results was significantly lower after the 3rd month of follow-up than that of patients who were partially or completely satisfied with the results There were also fewer patients with caffeine abuse among adherent patients Dry mouth and itching became the reason for treatment refusal in 6.3% and 5.1% of patients, respectively According to patients’ self-assessment of reasons for refusal or long-term break in treatment, the principal factors were medical (including pharmacological) and economic ones More than 76% of patients stated these factors Social and psychological factors comprised about 24% of answers Regression models allowed to determine the effect of some economic (annual and monthly salary, their square, and square of the percentage of expenses for trospium), sociological (age, professional occupation), and medical (treatment efficacy and satisfaction, side effects, the urination disorder form, severity of symptoms, and caffeine abuse) factors on patients’ adherence to treatment with trospium Therefore, according to data obtained, the maximum probability to preserve adherence to treatment with trospium during a year was observed in the elderly patients, who are education or healthcare employees, having a high salary and low percentage of expenses for trospium in the share of expenses, diagnosed with UUI or OAB, with severe incontinence symptoms, with objectively high efficacy of treatment administered and high self-assessment of its results, not experiencing side effects during treatment, and not abusing caffeine These results are consistent, in general, with data of other authors, who refer to prevalent significance of medical factors in adherence to treatment with trospium Particularly, according to their data, the average period for the refusal of treatment with AM drugs is 159 days, and the percentage of “survival” of adherence to treatment during years of follow-up is less than 8%.34 According to our data, the average period of reaching a 30-day break is 182 days, which is almost similar with that value but characterizes trospium particularly There are some data available in literature on unusually high level of adherence to treatment with trospium compared to other AM drugs.25 There is information available about treatment discontinuation due to unsatisfactory results and side effects in 89% of patients However, according to our data, only 14.5% of patients refused treatment with trospium or discontinued it because of intolerable side effects Many researches consider dry mouth, constipation, headache, and blurred vision as the most frequent adverse Please cite this article in press as: Kosilov KV, et al., Factors of adherence to treatment with trospium in employees, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.01.001 K.V Kosilov et al / Urological Science xxx (2017) 1e8 symptoms, resulting in the refusal of treatment with АМs.21 According to our data, symptoms such as rash, itching, and xeroderma (refusal of treatment in 5.1% of 13.2% patients), and dry mouth (refusal of further treatment in 6.3% of 12.1% patients) were reported most frequently throughout the sample Probably, the uncommon configuration of adverse effects is associated with the fact that the trospium molecule does not penetrate through the bloodebrain barrier and does not affect the central nervous system compared with other AMs Some neurourologic studies provide information that adherence of elderly patients is greater than perseverance in cohorts of young and middle-aged patients For example, adherence in the age group of 18e39 years is 20.9% and that in the age group of 70 years and older is more > 70% Our data support the conclusion that the mean age of the most persevering patients is 56.3 years Probably, this can be explained with greater motivation, financial capability, and severity of symptoms in middle-aged patients On the contrary, some investigators suggest that the adherence decreases due to increased comorbidity in elderly individuals.14 There are some data in literature sources on influence of factors, such as paying capacity, the mean cost of АМ drugs, duration of short-term disability leave, and absence at work due to sick leave, on adherence in patients receiving anticholinergic drugs in the cohort with adherence  80%.24 In our study, we also found correlation between monthly expenses for trospium and other drugs, purchased for treatment of comorbid conditions, level of annual and monthly salary, and patients’ adherence However, in contrast with the above source, according to our data, parameters such as disability cost, sick leave cost, sick leave days, constant work, full working day, employee turnover, and tenure (years with employers) in cohorts with different adherence levels have no significant differences Probably, this inconsistency can be explained by the use of different methodological approaches: in the above study, they used the method of retrograde analysis and account of drug administration based on prescriptions, while we preferred the design of prospective randomized observation with another standard of parameter recording Increased adherence level is also observed in case of free provision of AM drugs, which is indirectly consistent with the data obtained in our experiment In general, our data does not differ from the already known results However, in our experiment, we have used a comprehensive approach to study the issue trying to compare the significance of heterogeneous factors affecting patients’ adherence We tried to compare the significance of heterogeneous factors, such as medical, economic, and social ones, using standardized procedures, questionnaires, and highly specialized methods, thereby making the analysis more objective During a year, we observed a large cohort of patients receiving trospium; this allowed us to monitor, analyze, and compare the significance of different factors in dynamics Surely, the results we obtained are not conclusive; however, we believe that they may be of certain interest for practicing urologists, particularly, for the prediction of adherence to treatment with trospium in cohorts with different social, economic, and medical characteristics Limitations We have not studied all the factors that can affect patients’ adherence The factors preceding the beginning of the experiment, such as duration of the disease, duration and efficacy of treatment with other AM agents, use of non-medicinal methods of treatment, duration of comorbid conditions, and their treatment efficacy, remain beyond the scope of our study The severity of urodynamic disorders was monitored using voiding diaries, OABq-SF questionnaire, and uroflowmetry, which imposed some limitations on diagnostic accuracy Additional patients’ income, income of their families, and expenses apart from purchase of the drugs were not studied The analysis of adherence to treatment regarding other AM drugs, including prolonged-release agents, and other ways of LUTS treatment were not included in the scope of this study In our calculations, we did not consider the correlation between the cost of trospium and other drugs, purchased by patients, the percentage of these expenses in overall expenses of the patient and his family We excluded patients aged < 18 years and > 60 years from the study The study of influence of some factors variability in case of changes in some other parameters was not included in the protocol as well All these issues still require further consideration and would probably become a subject for our further studies Conclusion This study has demonstrated that some medical, social, and economic factors affect the adherence to treatment with trospium to some extent There were 56.1% of patients diagnosed with UUI and 40.7% with OAB, 56.1% patients with severe symptoms of incontinence, 25.3% with high treatment efficacy confirmed instrumentally, 57.5% of patients satisfied with treatment outcome, and only 5.5% patients refused treatment due to side effects among patients in the group with adherence level  80% The percentage of patients in the group with high adherence to treatment differed significantly in these parameters from the groups with moderate and poor adherence The mean age of the patients in the adherent group was 56.3 years This group included 25.0% of education employees, 32.5% of healthcare employees (significantly higher than in other groups), and 7.8% of retail employees (significantly lower than in other groups) The monthly and annual salary was significantly higher and the percentage of expenses for trospium and other drugs was significantly lower of adherent patients than the patients in other groups Patients from the group with high adherence at the end of treatment assessed health-related quality of life significantly higher The distribution of reasons for the refusal of treatment based on subjective patients’ reports did not significantly differ from the percentage of refusals obtained using questionnaires and objective study methods This study provides evidence of potential possibility to predict adherence during treatment with trospium and, probably, to manage the treatment efficacy Conflicts of interest There are no conflicts of interest among the authors References Irwin D, Kopp Z, Agatep B, Milsom I, Abrams P Worldwide prevalence estimates of lower urinary tract symptoms, overactive bladder, urinary incontinence and bladder outlet obstruction BJU Int 2011;108:1132e8 Coyne K, Zyczynski T, Margolis MK, Elinoff V, Roberts RG Validation of an overactive bladder awareness tool for use in primary care settings Adv Ther 2005;22:381e94 Sexton CC, Coyne KS, Thompson C, Bavendam T, Chen CI, Markland A Prevalence and effect on health-related quality of life of overactive bladder in older Americans: results from the epidemiology of lower urinary tract symptoms study J Am Geriatr Soc 2011;59:1465e70 Coyne KS, Margolis MK, Kopp ZS, Kaplan SA Racial differences in the prevalence of overactive bladder in the United States from the epidemiology of LUTS (EpiLUTS) study Urol 2012;79:95e101 Coyne KS, Sexton CC, Bell JA, Thompson CL, Dmochowski R, Bavendam T, et al The prevalence of lower urinary tract symptoms (LUTS) and overactive bladder (OAB) by racial/ethnic group and age: results from OAB-POLL Neurourol Urodyn 2013;32:230e7 Please cite this article in press as: Kosilov KV, et al., Factors of adherence to treatment with trospium in employees, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.01.001 K.V Kosilov et al / Urological Science xxx (2017) 1e8 re T, Kaufman L Overactive bladder symptoms, stress de Ridder D, Roumegue urinary incontinence and associated bother in women aged 40 and above; a Belgian epidemiological survey Int J Clin Pract 2013;67:198e204 como RH, Gomide LB, Garcia PA, Bontempo AP, Karnikoskwi MG Alves AT, Ja Relationship between anxiety and overactive bladder syndrome in older women Rev Bras Ginecol Obstet 2014;36:310e4 Coyne KS, Sexton CC, Thompson C, Kopp ZS, Milsom I, Kaplan SA The impact of OAB on sexual health in men and women: results from EpiLUTS J Sex Med 2011;8:1603e15 Coyne KS, Wein A, Nicholson S, Kvasz M, Chen CI, Milsom I Economic burden of urgency urinary incontinence in the United States: a systematic review J Manag Care Pharm 2014;20:130e40 10 Coyne KS, Sexton CC, Thompson CL, Clemens JQ, Chen CI, Bavendam T, et al Impact of overactive bladder on work productivity Urol 2012;80:97e103 11 Wu EQ, Birnbaum H, Marynchenko M, Mareva M, Williamson T, Mallett D Employees with overactive bladder: work loss burden J Occup Environ Med 2005;47:439e46 12 Andersson KE Antimuscarinics for treatment of overactive bladder Lancet Neurology 2004:46e53 13 Andersson KE New developments in the management of overactive bladder: focus on mirabegron and onabotulinumtoxinA Ther Clin Risk Manag 2013;9: 161e70 14 Mauseth SA, Skurtveit S, Spigse TO Adherence, persistence and switch rates for anticholinergic drugs used for overactive bladder in women: data from the Norwegian Prescription Database Acta Obstet Gyn Scand 2013;92:1208e15 15 Kosilov K, Loparev S, Ivanovskaya M, Kosilova L Effectiveness of combined high-dosed trospium and solifenacin depending on severity of OAB symptoms in elderly men and women under cyclic therapy Cent European J Urol 2014;67: 43e8 16 Kosilov K, Loparev S, Ivanovskaya M, Kosilova L Randomized controlled trial of cyclic and continuous therapy with trospium and solifenacin combination for severe overactive bladder in elderly patients with regard to patient compliance Ther Adv in Urol 2014;6:215e23 17 Kosilov KV, Loparev SA, Ivanovskaya MA, Kosilova LV Comparative effectiveness of combined high-dosed Trospium and Solifenacin for severe OAB symptoms in age-related aspect Int J Urol Nurs 2015;9:108e13 18 Veenboer PW, Bosch JL Long-term adherence to antimuscarinic therapy in everyday practice: a systematic review J Urol 2014;191:1003e8 19 Basra RK, Wagg A, Chapple C, Cardozo L, Castro-Diaz D, Pons ME, et al A review of adherence to drug therapy in patients with overactive bladder BJU Int 2008;102:774e9 20 Benner JS, Nichol MB, Rovner ES, Jumadilova Z, Alvir J, Hussein M, et al Patientreported reasons for discontinuing overactive bladder medication BJU Int 2009;105:1276e82 21 Oefelein MG Safety and tolerability profiles of anticholinergic agents used for the treatment of overactive bladder Drug Saf 2011;34:733e54 22 Yeaw J, Benner JS, Walt JG, Sian S, Smith DB Comparing adherence and persistence across chronic medication classes J Manag Care Pharm 2009;15: 728e40 23 Brostrøm S, Hallas J Persistence of antimuscarinic drug use Eur J Clin Parmacol 2009;65:309e14 24 Kleinman NL, Odell K, Chen CI, Atkinson A, Zou KH Persistence and adherence with urinary antispasmodic medications among employees and the impact of adherence on costs and absenteeism J Manag Care Pharm 2014;20: 1047e56 25 Biastre K, Burnakis T Trospium chloride treatment of overactive bladder Ann Pharmacother 2009;43:283e95 26 Thüroff JW, Abrams P, Andersson KE, Artibani W, Chapple CR, Drake MJ, et al EAU guidelines on urinary incontinence Eur Urol 2011;59:387e400 27 Coyne K, Thompson C, Lai J, Sexton C An overactive bladder symptom and health-related quality of life short-form: validation of the OAB-q SF Neurourol Urodyn 2015;34:255e63 28 Yang M, Wang H, Wang J, Ruan M Impact of invasive bladder cancer and orthotopic urinary diversion on general health-related quality of life: an SF-36 survey Mol Clin Oncol 2013;1:758e62 29 Seckiner I, Yesilli C, Mungan NA, Aykanat A, Akduman B Correlations between the ICIQ-SF score and urodynamic findings Neurourol Urodyn 2007;26:492e4 30 Jin J, Sklar GE, Oh VM, Li SC Factors affecting therapeutic compliance: a review from the patient's perspective Ther Clin Risk Manag 2008;4:269e86 31 Cano-Marquina A, Tarín JJ, Cano A The impact of coffee on health The Eur Menop Journ 2013;75:7e21 32 Raupach T, Brown J, Herbec A, Brose L, West R A systematic review of studies assessing the association between adherence to smoking cessation medication and treatment success Addiction 2014;109:35e43 33 Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M Development of the Alcohol Use Disorders Identification Test (AUDIT): WHO Collaborative Project on Early Detection of Persons with Harmful Alcohol Consumption-II Addiction 1993;88:791e804 34 Chancellor MB, Migliaccio-Walle K, Bramley TJ, Chaudhari SL, Corbell C, Globe D Long-term patterns of use and treatment failure with anticholinergic agents for overactive bladder Clin Ther 2013;35:1744e51 Please cite this article in press as: Kosilov KV, et al., Factors of adherence to treatment with trospium in employees, Urological Science (2017), http://dx.doi.org/10.1016/j.urols.2017.01.001 ... the purpose of this study was to study the significance of the factors affecting adherence to treatment with trospium in the cohort of employees to increase the efficacy of management of various... severity of symptoms, and caffeine abuse) factors on patients’ adherence to treatment with trospium Therefore, according to data obtained, the maximum probability to preserve adherence to treatment with. .. individuals with the level of income lower than the living minimum wage; number of sick leave Please cite this article in press as: Kosilov KV, et al., Factors of adherence to treatment with trospium in