factors of adherence to treatment with trospium in employees

Patients diagnosed with urge urinary incontinence and overactive bladder OAB 56.1%; 40.7%, having severe incontinence symptoms 56.1%, showing objectively high treatment effi-cacy 25.3%, a

Original article

Factors of adherence to treatment with trospium in employees

Kirill Vladimirovich Kosilova,b,*, Sergay Alexandrovich Loparevc,

a r t i c l e i n f o

Article history:

Received 2 June 2016

Received in revised form

25 September 2016

Accepted 1 January 2017

Available online xxx

Keywords:

adherence of treatment

employees

incontinence

lower urinary tract symptoms

trospium

a b s t r a c t 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 de-mographic, socioeconomic, and medical parameters by studying employer’s records, extracts from in-come 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 6 months and 12 months, respectively The average time of reaching a 30-day break in trospium admin-istration 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 effi-cacy (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 signifi-cantly 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 thefirst time the determination of the complexity of hetero-geneous 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/)

1 Introduction

The prevalence rates of lower urinary tract symptoms (LUTS)

and, particularly, overactive bladder (OAB) symptoms remain

consistently high worldwide.1,2The prevalence ofОАВ is

signifi-cantly 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

LUTS are often accompanied with depression, anxiety, decreased mental and physical activity, social isolation, and sexual health problems.7,8Apart 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 in-dividuals suffering from asthma or chronic arthritis.9e11

Efficacy and safety of the available range of antimuscarinic drugs (AM) is generally recognized at the moment.12Additionally, 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

* Corresponding author Ayax 10, F733, DVFU, Vladivostok, RUVVO, Russian

Federation.

Contents lists available atScienceDirect Urological Science

j o u r n a l h o m e p a g e :w w w u r o l - s c i c o m

http://dx.doi.org/10.1016/j.urols.2017.01.001

creativecommons.org/licenses/by-nc-nd/4.0/ ).

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.19,20We have established correlation between adherence to

prescriptions and efficacy of AMs, development of side effects, a

regimen and a method ofАМadministration, and pharmacology of

different drugs Sometimes the results of the studies differ signi

fi-cantly among different authors For example, in one of the studies, it

was found that adherence to treatment with fesoterodine is

signif-icantly higher than that with solifenacine and lolnerodinum.21In

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

certainАМdrug and a wide range of medical, pharmacodynamic,

socioeconomic, and demographic factors that could affect the

pa-tient’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

someАМdrugs, particularly trospium, of decreased and increased

dosage, on the activity ofОАВ symptoms Trospium chloride is a

quaternary ammonium compound, which does not affect the

cen-tral nervous system and causes no side effects, associated with

influence on the central nervous system.25We 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 signi

fi-cance of the factors affecting adherence to treatment with trospium

in the cohort of employees to increase the efficacy of management

of various LUTS forms

2 Methods

2.1 Background information about the experiment

The study design is presented inFigure 1 The study was

con-ducted at the premises of the Regional Diagnostics Center of the

City Polyclinic No 3 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

odd-numbered days of the month and prescribed with a long-term (>

1 year) treatment with trospium only.25Selection 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 2 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-9-CM: 788.43 converts directly to 2015 ICD-10-CM R35.1).26 The diagnosis was confirmed by the data from voiding diaries, ques-tionnaires OAB questionnaire short form (OABq-SF), and results of uroflowmetry.27

Furthermore, the criteria for inclusion in the group were employment for at least 6 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

6 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 mono-therapy 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 ep-isodes, 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 caffein-ated food and drinks as well as alcohol

Before the study, after the 6thmonth (1stcheckpoint) and in the end of the follow-up period (2ndcheckpoint), all patients under-went the following diagnostic procedures: (1) uroflowmetry, evaluation of urodynamics during the evacuation phase with calculation of urine volume (mL), average urineflow rate (Qaver, mL/ s), maximum urineflow rate (Qmax, mL/s), which provides objective evaluation of urination disorders; (2) completion of the question-naire OABq-SF to specify the form and severity of urination disor-ders; a score of> 8 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 char-acterizing a certain aspect of quality of life: physical functioning (PF), role-physical (RР), bodily pain (ВP), general health (GH), vi-tality (VT), social functioning (SF), role-emotional (RE), and mental health (MH) The scale ranges from 0 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 ques-tionnaires, containing information about main descriptive de-mographic 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 dis-order, 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 manufac-turers does not exceed 300 mg.31Smoking of more thanfive ciga-rettes a day was defined as tobacco abuse, and the score > 8 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

K.V Kosilov et al / Urological Science xxx (2017) 1e8 2

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 5 years before the experiment, and time of work at one place The level of salary and expenses pre-sented are adjusted for inflation to the price of the US dollar as of June 2012

499.3 534.8

598.5

659.7

705.6 748.6 855.3 959.1 1068.6 1193.5

450

550

650

750

850

950

1050

1150

1250

10 20 30 40 50 60 70 80 90

Proportion of day covered (%)

9.2

8.4

7.7 7.1

6.3 5.9

5.2 5.1 4.8 4.5

4

5

6

7

8

9

10

10 20 30 40 50 60 70 80 90

Proportion of day covered (%)

Figure 1 (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

98.3

94.2

86.1 81.5 78 76.9 73.4

64.7 60.7 57.2 56.1 56.1

98.1

82.3

71.5 63.1 60.6 59.1

56.1

40.7

93.1

67.5

60.7 47 38.5

19.6 16.2

12.8 9.4 7.7

96.5

65.2

53

42.6 30.4

26.1 22.6

16.5 11.3

13.9 8.7 4.3 0

10 20 30 40 50 60 70 80 90 100

months

Urge incontinence (n=173) Overactive bladder (n=572) Mixed incontinence (n=117) Nocturnal incontinence (n=115)

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

po-tential affecting factor

The average level of patient’s adherence was defined as the

percentage of days during the year from the beginning of

sol-ifenacin 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

three-parameter 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 1 censoring

Goodness offit 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

eco-nomic factors, including the diagnosis form, severity of symptoms

and side effects, objective and subjective treatment outcome,

presence of bad habits, comorbidity, experience of use ofАМdrugs,

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

3 Results

In total, the proportion of patients who were able to preserve

adherence to treatment were 70.6% during thefirst 3 months (1st

checkpoint), 54.4% during 6 months, and 35.5% at the end of the

experiment (2ndcheckpoint) The mean time of reaching a 30-day

break in trospium administration was 182 days

Table 1 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

pa-tients [56.3 (5.9)] proved to be higher than the age of the papa-tients

with moderate and low level of adherence to treatment with

trospium ( 0.05;  0.05) The percentage of healthcare or edu-cation 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 mod-erate (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 per-centage of monthly expenses for trospium in the group with high adherence was lower than that in the non-adherent group

Figure 1demonstrates increased patients’ adherence upon in-crease of their monthly salary and dein-crease of the percentage of expenses for trospium Analyzing the regression model of salary-adherence correlation, we found that the influence of annual salary and its square on patients’ adherence was direct and signif-icant (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 sta-tistical homogeneity in the cohorts

At thefirst 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 2shows 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 per-centage of adherent patients (56.1%) with severe incontinence (episode of UI 3/day) was significantly higher than that of pa-tients with moderate adherence level (31.2%; p 0.01) and non-adherent 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 re-sults to each other It was found that the above factors have a

sig-nificant 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 pa-tients 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 experi-ment were significantly higher (lower scores) than in other groups (p 0.05; p  0.05) Analysis of the results of urodynamics evalu-ation with voiding diaries showed almost similar results According

to uroflowmetry data, in the group of adherent patients, bladder

K.V Kosilov et al / Urological Science xxx (2017) 1e8 4

Table 1

< 50%

Adherence

 50%, < 80% (n ¼ 430)

p

Field of activity:

Remark.

Table 2

< 50%

Adherence

50%, < 80% (n ¼ 430)

p

Bad habits:

AM¼ 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

person.

checkpoint) of observation.

volume and maximum urineflow rate characterizing accumulative

and evacuation functions have changed significantly The

percent-age 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 2demonstrates 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

per-centage 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 r¼ 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 5thmonth 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  3 decreased

smoothly during the whole follow-up period, while the percentage

of patients with moderate symptoms decreased dramatically from

the 2ndto 4-5thmonths The curves, describing the change of the

percentage of adherent patients, demonstrate the level of direct

correlation r¼ 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

psycho-logical factors was 15% (more than a half of them were negative

experience of treatment with AMs) Also, 9% of patients stated

so-cial 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

sig-nificant 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

per-centage of patients who refused treatment because of these

symptoms differed significantly in the groups with different

adherence levels (p 0.05)

4 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

experi-ment was also significantly higher than that in other groups

Studying medical factors influencing the adherence, we

estab-lished 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 physi-cian’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 3 episodes/day) among pa-tients with UUI In turn, papa-tients 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 ma-jority 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 pa-tients, 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, pro-fessional occupation), and medical (treatment efficacy and satis-faction, 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 au-thors, 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 2 years of follow-up is less than 8%.34According

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

K.V Kosilov et al / Urological Science xxx (2017) 1e8 6

symptoms, resulting in the refusal of treatment withАМs.21

Ac-cording 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

re-ported most frequently throughout the sample Probably, the

un-common 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 ofАМdrugs, 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%.24In our study, we also found

cor-relation 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

em-ployers) in cohorts with different adherence levels have no

signif-icant 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

stan-dard 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

comprehen-sive 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,

ques-tionnaires, 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

5 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

ques-tionnaire, 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

6 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

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