- Email: [email protected]
Translation, cross-cultural adaptation, and validation of the Bulgarian version of the Liverpool Adverse Event Profile
Epilepsy & Behavior 39 (2014) 88–91
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Brief Communication
Translation, cross-cultural adaptation, and validation of the Bulgarian version of the Liverpool Adverse Event Profile Rumyana Kuzmanova a,⁎, Irina Stefanova a, Irena Velcheva a, Katerina Stambolieva b a b
University Hospital of Neurology and Psychiatry “St. Naum”, Sofia, Bulgaria Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
a r t i c l e
i n f o
Article history: Received 26 July 2014 Revised 20 August 2014 Accepted 21 August 2014 Available online 18 September 2014 Keywords: Liverpool Adverse Event Profile Epilepsy Quality of Life in Epilepsy Inventory
a b s t r a c t Background: Adverse effects (AEs) of antiepileptic drugs (AEDs) affect the quality of life of patients with epilepsy and their outcomes. There are no questionnaires or studies on the reliability and validity of instruments measuring AEs of AEDs in patients with epilepsy in Bulgarian language. Purpose: The aim of the present study was the translation, cross-cultural adaptation, and validation of the LAEP in the Bulgarian language in order to use it in the Bulgarian-speaking population in providing a reliable instrument for the clinical monitoring of patients with epilepsy. Methods: One hundred thirty-one patients (57 men and 74 women, mean age: 40.13 ± 13.37 years) took part in the investigation. The internal consistency and test–retest reliability were tested by Cronbach's α and ICC estimations. The convergent construct validity was tested by estimating the correlation of the LAEP-BG with the QOLIE-89 and the discriminant validity by evaluating the difference between LAEP-BG scores and clinical parameters such as the type of epilepsy using Kruskal–Wallis ANOVA. Results: The LAEP-BG showed high internal consistency and reliability. The Cronbach's α of the total scale was 0.86. No significant differences between the Cronbach's α coefficients of the total LAEP-BG and original English, Chinese, Spanish, Korean, and Portuguese–Brazilian versions of the questionnaire were observed. The ICCs, which evaluate the test–retest reliability, were higher than the recommended value of 0.75 and determined the strong positive correlations between the first and second examinations. The creation of two subscales “Neurological and psychiatric side effects” and “Non neurological side effects” of the LAEP-BG proposed by us showed good internal consistency (Cronbach's α of 0.85 and 0.71, respectively). The LAEP-BG scores significantly correlated with other questionnaires such as the Quality of Life in Epilepsy Inventory—89 (QOLIE-89) and showed a good discriminative validity between groups with different levels of self-assessed AEs of AEDs. Conclusion: The Bulgarian version of the Liverpool Adverse Event Profile (LAEP) is a reliable and valid tool in assessing the patient-reported AEs of AEDs and their impact on the patient's outcome. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Epilepsy is a multifaceted chronic disorder with diverse and complex effects on the QOL of the patient [1]. High rates of AEs and intolerability of AEDs are important predictors of poor QOL in epilepsy and patients' outcome [2]. There are many studies on AEs of AEDs and instruments used to evaluate them [3–9]. According to the literature, the LAEP questionnaire is one of the standardized instruments to assess patient-reported AEs of AEDs. The LAEP is an instrument to measure the total side effects of a medication regimen and to quantify patients' perceptions of the most common negative side effects of AED treatment [3,10]. There are valid and available versions of the
⁎ Corresponding author at: University Hospital of Neurology and Psychiatry “St. Naum”, Louben Russev str., 1, 1113 Sofia, Bulgaria. Tel.: +359 2 9702216; fax: +359 2 8700036. E-mail address: [email protected] (R. Kuzmanova).
http://dx.doi.org/10.1016/j.yebeh.2014.08.124 1525-5050/© 2014 Elsevier Inc. All rights reserved.
LAEP in the English, Spanish, Chinese, Korean, and Portuguese languages [3,11–14]. Questionnaires or studies on the reliability and validity of instruments measuring AEs of AEDs in patients with epilepsy in Bulgarian language do not exist. The aim of the present study was the translation, cross-cultural adaptation, and validation of the LAEP in the Bulgarian language in order to use it in the Bulgarian-speaking population in providing a reliable instrument for the clinical monitoring of patients with epilepsy. 2. Methods The study group consisted of 131 consecutively enrolled patients out of a total of 449 screened patients from the Epilepsy Department of the University Hospital of Neurology and Psychiatry “St. Naum”, Sofia, Bulgaria. The patient selection was based on several criteria: (1) diagnosis of epilepsy according to the ILAE criteria for more than 1 year; (2) age of more than 18 years; (3) lack of cognitive impairment, tested with a Mini-
R. Kuzmanova et al. / Epilepsy & Behavior 39 (2014) 88–91
Mental State Examination score ≥ 28 when used as a screening scale, and sufficient reading ability; and (4) stable doses of antiepileptic drugs (AEDs) for at least 3 months prior to study entry. Patients with another progressive neurological or psychiatric disease or some other chronic severe physical comorbidity (diabetes, asthma, or heart, renal, or hepatic failure, etc.) on stable concomitant medication were excluded from the investigation. All subjects were volunteers and gave a signed informed consent to participate in the study, which was approved by the local Ethics Committee of Medical University — Sofia and conducted in accordance with the ethical standards of the Declaration of Helsinki. The participants were free to withdraw from the study at any time. All patients were asked to fill out two questionnaires: the LAEP-BG scale and the Bulgarian version of the QOLIE-89 questionnaire validated by Viteva et al. [15]. The Bulgarian version of the QOLIE-89 consists of 89 questions divided into seventeen domains: seizure worry, medication effects, health perceptions, health discouragement, work/driving/social function, language, attention/concentration, memory, overall QOL, emotional well-being, role limitations: emotional, role limitations: physical, social isolation, social support, energy/fatigue, physical functioning, and pain. The original LAEP scale consists of 19 questions that are presented as a checklist of symptoms experienced in the past 4 weeks, rated using Likert scale responses [16]. With the consent of the author, the original English version of the LAEP questionnaire was translated into Bulgarian by two independent medical experts with very good knowledge of English and good experience in adaptation of clinical tests. It was afterwards retranslated into English by two independent translators who were unaware of the original LAEP version. No major differences between the two translations were found. In order to identify problems in comprehension or cultural specificities, the preliminary Bulgarian version of the LAEP which was edited according to the rules of the Bulgarian language was administered to a pilot sample of ten patients with epilepsy attending the clinic. All questions were well-accepted. The patients filled in the final questionnaire in the hospital in our presence. They understood all the items and did not find any difficulty in answering the questions. After performing and evaluating the pilot study, we came to the conclusion that three of the items should be modified so that the inventory would become better for our purpose. First, we observed that the word “unsteadiness” had to be changed to “instability”. Second, the word “aggression” was replaced by “feeling of anger or aggression”. Third, “nervousness” was replaced by “nervousness and/or agitation”. The panel of the same experts who participated in the previous phase discussed that no further adaptations were required. Descriptive statistics were used for calculating the mean scores of the LAEP scale and demographic data. The score distribution of each item was evaluated for investigating the possible ceiling and floor effects (proportions of patients with the best and worst possible scores). The internal consistency of the LAEP scale was determined by estimating the Cronbach's α coefficient. In general, Cronbach's α N 0.7 (Nunnally's criterion) indicates high levels of internal consistency [17–19]. The test–retest reliability was evaluated by calculating ICCs. In general, values above 0.75 are indicative of reliability. The Mann–Whitney U-tests were used for the estimation of differences between correlation coefficients of items in Bulgarian and other language versions of the scale, where the correlation coefficients were transformed by Fisher transformation. The convergent construct validity was tested by estimating the correlation of the LAEP-BG with the QOLIE-89 and the discriminant validity by evaluating the difference between LAEP-BG scores and clinical parameters such as the type of epilepsy using Kruskal–Wallis ANOVA. The analyses were made using the computer software Statistica 8.0 for Windows (StatSoft Inc., USA).
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3. Results The average age of the patients was 40.13 ± 13.37 years, the mean duration of the disease was 15.61 ± 9.45 years, 43.5% were male, and the education level of 89% was relatively high (secondary school — 52% and university education — 37%). The patients with idiopathic epilepsy comprised 19.8% of the sample, with cryptogenic epilepsy 45.8%, and with symptomatic epilepsy 34.4%. All patients completed the LEAP questionnaire manually, and missing information on any of the items was not observed (analysis of missing data not supplied). The patients declared that all questions were clearly defined and that they had not encountered difficulties in completing the questionnaire. We used the original questionnaire with 19 items and created three subscales of items in accordance with the classification of Chen et al. [12]: “CNS dose-related side effects,” “Non CNS dose-related side effects,” and “Psychiatric side effects.” The “CNS dose-related side effects” subscale contained 10 items: unsteadiness, tiredness, headache, double/ blurred vision, difficulty in concentrating, shaky hands, dizziness, sleepiness, memory problems, and disturbed sleep (theoretical summary score range of 10–40 points). The “Non CNS dose-related side effects” subscale consisted of 5 items: hair loss, skin problems, upset stomach, trouble with mouth/gums, and weight gain (theoretical score range of 5–20 points) and “Psychiatric side effects” 4 items: restlessness, feelings of aggression, nervousness/agitation, and depression (theoretical score range of 4–16 points). The Cronbach's α of the total scale was 0.86, which indicates high levels of internal consistency. The Cronbach's α values of the three subscales were as follows: “CNS dose-related side effects” — 0.85, “Non CNS dose-related side effects” — 0.71, and “Psychiatric side effects” — 0.44. The Cronbach's α of the third subscale was b 0.7 and showed a low internal reliability of this subscale. That was the reason for creating two subscales of the LAEP-BG: the first one consisted of the “CNS dose-related side effects” and “Psychiatric side effects”, which are united and named “Neurological and psychiatric side effects” (14 items, theoretical score range of 14–56 points) and the second subscale was the “Non neurological side effects” (5 items, theoretical score range of 5–20 points). The two subscales had good internal reliability. The Cronbach's α for the “Neurological and psychiatric side effects” subscale was 0.85 and for the “Non neurological side effects” subscale 0.71. No significant differences were observed between the Cronbach's α coefficients of the total scale of LAEP-BG and original English (0.89) [3], Chinese (0.92) [12], Spanish (0.84) [11], Korean (0.9) [13], and Portuguese–Brazilian (0.9) [14] versions of the questionnaire. The range of observed scores was 19–66 (theoretical range: 19–76). Out of 131 patients, 2% had a score of 19 points and 1% had a score of 66 points. Forty-three percent had a score higher than 45 points. The results demonstrated no obvious floor and ceiling effects. The mean scores, medians, and test–retest reliability of the LAEP-BG determined with the ICCs were presented in Table 1. The ICCs, which evaluate the test–retest reliability, were higher than the recommended value of 0.75 and showed strong positive correlations between the first and second examinations, which prove the reliability of the scale (Table 1). The convergent construct validity of the LAEP-BG scores for the “Neurological and psychiatric side effects” subscale was high, which demonstrates good reliability of the results related to this category of negative effects of the disease (Table 2). The Kruskal–Wallis ANOVA with three levels (idiopathic, cryptogenic, and symptomatic types of epilepsy) showed a significant effect in relation to the type of epilepsy on the LAEP-BG total score (H(2,131) = 6.552, p b 0.05). A post hoc Mann–Whitney U-test showed a significant difference of the total LAEP-BG scores between patients with idiopathic and symptomatic types of epilepsy (p b 0.05). The results suggest that LAEP-BG score shows good discriminative validity between groups with different types of epilepsy.
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R. Kuzmanova et al. / Epilepsy & Behavior 39 (2014) 88–91
Table 1 The mean scores, medians, and test–retest reliability (ICCs) of the LAEP-BG (n = 131). Items
Median (range)
Mean (SD)
ICC
Unsteadiness Tiredness Restlessness Feelings of anger or aggression to others Nervousness and/or agitation Headache Hair loss Problems with skin (acne, rash) Double or blurred vision Upset stomach Difficulty in concentrating Trouble with mouth or gums Shaky hands Weight gain Dizziness Sleepiness Depression Memory problems Disturbed sleep Overall score Neurological and psychiatric side effects Non neurological side effects
3 (1–4) 3 (1–4) 3 (1–4) 2 (1–4) 2 (1–4) 3 (1–4) 2 (1–4) 1 (1–4) 2 (1–4) 1 (1–4) 2 (1–4) 1 (1–4) 2 (1–4) 2 (1–4) 3 (1–4) 3 (1–4) 2 (1–4) 3 (1–4) 2 (1–4) 45 (28–60) 34 (14–49) 9 (5–20)
2.47 (1.04) 2.60 (0.96) 2.49 (0.96) 1.94 (0.95) 2.32 (0.89) 2.45 (0.99) 1.93 (1.04) 1.66 (0.99) 2.1 (1.03) 1.62 (0.74) 2.37 (0.87) 1.85 (1.08) 2.34 (1.04) 2.35 (1.15) 2.47 (0.97) 2.55 (1.03) 2.02 (0.91) 2.55 (1.02) 2.15 (1.06) 47.75 (7.82) 32.82 (7.86) 9.42 (3.17)
0.96 0.94 0.95 0.93 0.93 0.95 0.90 0.79 0.91 0.97 0.89 0.79 0.83 0.77 0.94 0.94 0.97 0.93 0.93 0.96 0.93 0.91
(0.89), Spanish version (0.84), Chinese version (0.92), Korean version (0.9), and Portuguese–Brazilian version (0.9) [3,11–14]. In the LAEP-BG, the subscale “Psychiatric side effects”, created in accordance with Chen et al. [12], showed low internal consistency (Cronbach's α = 0.44). This may be partially explained by minimum cross-cultural differences. The result gave us a reason to create the two subscales: “Neurological and psychiatric side effects” consisting of 14 items and “Non CNS dose-related side effects” consisting of 5 items, which showed high internal consistency (Cronbach's α of 0.85 and 0.71, respectively). The most important finding for the Bulgarian population were the questions pertained to the neurological and psychiatric effects of AEDs, suggesting that neurotoxic symptoms are of high significance and affect the overall QOL. This result is similar to the most common reported AEs in a study of Baker et al. [10] wherein N50% of patients reported problems with attention, concentration, memory, and fatigue [7]. There are several limitations of the current study. The main limitation of our work is that the patient sample was drawn from epilepsy clinics at a university hospital and these subjects might not be representative of patients with epilepsy in the general population. An additional study limitation includes the lack of an independent control group. Adverse effects were self-reported by the patients, and their answers could be influenced by sociocultural and environmental factors.
4. Discussion 5. Conclusion The clinical monitoring of AEs of AEDs in Bulgaria is usually underperformed, and the outcome assessment in patients with epilepsy is traditionally focused on the reduction of seizures. The LAEP-BG questionnaire is the first questionnaire assessing the patient's reported AEs of AEDs in the Bulgerian language. Our results showed that the Bulgarian version of the LAEP questionnaire is well-understood, well-accepted, short and flexible, and easy for patients to answer. The demographic and clinical characteristics of the patients enrolled in this study do not differ from those used in other language versions of the scale, and the results were similar as well. The results of the present study show that the LAEP-BG questionnaire has good reliability and validity. The Cronbach's α of the total scale is 0.86 (required criteria: α ≥ 0.8) which indicates high levels of internal consistency and similarity with other language versions of the scale: original English version
The results of this study confirm the psychometric properties of the Bulgarian version of the LAEP and provide the scientific basis for the utilization of the questionnaire for assessing the self-reported AEs of AEDs and their impact on the patient's outcome. Further investigation is needed to examine the sensitivity of the LAEP-BG to clinical change, which should be of benefit to medical practice. Acknowledgment We would like to thank Prof. Baker for his permission and encouragement for validating the questionnaire. Conflict of interest The authors declare that they have no conflicts of interest and report that this is an original paper that has not been submitted elsewhere.
Table 2 Correlations between LAEP-BG scores divided into two subscales and 17 subscales of the QOLIE-89 (n = 131). QOLIE-89
Neurological and psychiatric side effects
Non neurological side effects
Health perceptions Overall quality of life Physical function Role limitations: physical Role limitations: emotional Pain Work/driving/social function Energy/fatigue Emotional well-being Attention/concentration Health discouragement Seizure worry Memory Language Medication effects Social support Social isolation Overall health
−0.461⁎⁎ −0.411⁎⁎ −0.534⁎⁎ −0.549⁎⁎ −0.437⁎⁎ −0.303⁎⁎ −0.574⁎⁎ −0.493⁎⁎ −0.521⁎⁎ −0.601⁎⁎ −0.498⁎⁎ −0.326⁎⁎ −0.491⁎⁎ −0.432⁎⁎ −0.388⁎⁎ −0.204⁎ −0.291⁎ −0.661⁎⁎
−0.214⁎ −0.265⁎⁎ −0.219⁎ NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS
NS — no statistical significance. ⁎ Statistical significance of Spearman's correlation coefficient at p b 0.05. ⁎⁎ Statistical significance of Spearman's correlation coefficient at p b 0.001.
References [1] Auriel E, Landov H, Blatt I, Theitler J, Gandelman-Marton R, Chistik V, et al. Quality of life in seizure-free patients with epilepsy on monotherapy. Epilepsy Behav 2009;14: 130–3. [2] Cramer JA, Brandenburg NA, Xu X, Vera-Llonch M, Oster G. The impact of seizures and adverse effects on global health ratings. Epilepsy Behav 2007;11:179–84. [3] Baker GA, Frances P, Middleton A, Jacoby A, Schapel GJ, Defalla B. Initial development, reliability, and validity of a patient-based adverse event scale. Epilepsia 1994;35(Suppl. 7):S80. [4] Fisher RS, Vickrey BG, Gibson P, Hermann B, Penovich P, Scherer A, et al. The impact of epilepsy from the patient's perspective II: views about therapy and health care. Epilepsy Res 2000;41:53–61. [5] Gilliam F. Optimizing health outcomes in active epilepsy. Neurology 2002;58(Suppl. 5):9–19. [6] Luoni C, Bisulli F, Canevini MP, De Sarro G, Fattore C, Galimberti CA, et al. Determinants of health-related quality of life in pharmacoresistant epilepsy: results from a large multicenter study of consecutively enrolled patients using validated quantitative assessments. Epilepsia 2011;52:2181–91. [7] May TW, Brandt C, Kassel J. Evaluation of a self-report questionnaire for the assessment of adverse effects of antiepileptic drugs. Epilepsia 2009;50(Suppl. 4):104. [8] Perucca P, Carter J, Vahle V, Gilliam FG. Adverse antiepileptic drug effects: toward a clinically and neurobiologically relevant taxonomy. Neurology 2009;72:1223–9. [9] Taylor RS, Sander JW, Taylor RJ, Baker GA. Predictors of health related quality of life and costs in adults with epilepsy: a systematic review. Epilepsia 2011;52(12): 2168–80. [10] Baker GA, Jacoby A, Francis P, Chadwick DW. The Liverpool adverse drug events profile. Epilepsia 1995;36(Suppl. 3):S59.
R. Kuzmanova et al. / Epilepsy & Behavior 39 (2014) 88–91 [11] Carreno M, Donaire A, Falip M, Maestro I, Fernandez S, Nagel AG, et al. Validation of the Spanish version of the Liverpool Adverse Events Profile in patients with epilepsy. Epilepsy Behav 2009;15:154–9. [12] Chen HF, Tsai YF, Shih MS, Chen JC. Validation of the Chinese version of the Liverpool Adverse Events Profile in patients with epilepsy. Epilepsy Res 2011;94:45–52. [13] Park Jin-Mo, Seo Jong-Geun, Park Sung-Pa. Validity and reliability of the Korean version of the Liverpool Adverse Events Profile (K-LAEP) in people with epilepsy. J Korean Epilepsy Soc 2012;16(2):43–8. [14] Martins HH, Alonso NB, Vidal-Dourado M, Carbonel TD, de Araujo Filho GM, Caboclo LO, et al. Are adverse effects of antiepileptic drugs different in symptomatic partial and idiopathic generalized epilepsies? The Portuguese–Brazilian validation of the Liverpool Adverse Events Profile. Epilepsy Behav 2011;22:511–7.
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[15] Viteva EI, Zachariev ZI, Semerdzhieva MA. Validation of the Bulgarian version of the quality of life in epilepsy inventory (QOLIE-89). Folia Med (Plovdiv) 2010;52(1): 34–9. [16] Nixon А, Kerr C, Breheny K, Wild D. Patient Reported Outcome (PRO) assessment in epilepsy: a review of epilepsy-specific PROs according to the Food and Drug Administration (FDA) regulatory requirements. Health Qual Life Outcomes 2013;11:38. [17] Cronbach LJ. Coefficient alpha and the internal structure of tests. Psychometrika 1951;16:297–334. [18] Gill-Body KM, Beniato M, Krebs DE. Relationship among balance impairments, functional performance, and disability in people with peripheral vestibular hypofunction. Phys Ther 2000;80:748–58. [19] Nunnally JC. Psychometric theory. 3rd ed. New York: Basic Books; 1994. p. 265.
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Brief Communication
Translation, cross-cultural adaptation, and validation of the Bulgarian version of the Liverpool Adverse Event Profile Rumyana Kuzmanova a,⁎, Irina Stefanova a, Irena Velcheva a, Katerina Stambolieva b a b
University Hospital of Neurology and Psychiatry “St. Naum”, Sofia, Bulgaria Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria
a r t i c l e
i n f o
Article history: Received 26 July 2014 Revised 20 August 2014 Accepted 21 August 2014 Available online 18 September 2014 Keywords: Liverpool Adverse Event Profile Epilepsy Quality of Life in Epilepsy Inventory
a b s t r a c t Background: Adverse effects (AEs) of antiepileptic drugs (AEDs) affect the quality of life of patients with epilepsy and their outcomes. There are no questionnaires or studies on the reliability and validity of instruments measuring AEs of AEDs in patients with epilepsy in Bulgarian language. Purpose: The aim of the present study was the translation, cross-cultural adaptation, and validation of the LAEP in the Bulgarian language in order to use it in the Bulgarian-speaking population in providing a reliable instrument for the clinical monitoring of patients with epilepsy. Methods: One hundred thirty-one patients (57 men and 74 women, mean age: 40.13 ± 13.37 years) took part in the investigation. The internal consistency and test–retest reliability were tested by Cronbach's α and ICC estimations. The convergent construct validity was tested by estimating the correlation of the LAEP-BG with the QOLIE-89 and the discriminant validity by evaluating the difference between LAEP-BG scores and clinical parameters such as the type of epilepsy using Kruskal–Wallis ANOVA. Results: The LAEP-BG showed high internal consistency and reliability. The Cronbach's α of the total scale was 0.86. No significant differences between the Cronbach's α coefficients of the total LAEP-BG and original English, Chinese, Spanish, Korean, and Portuguese–Brazilian versions of the questionnaire were observed. The ICCs, which evaluate the test–retest reliability, were higher than the recommended value of 0.75 and determined the strong positive correlations between the first and second examinations. The creation of two subscales “Neurological and psychiatric side effects” and “Non neurological side effects” of the LAEP-BG proposed by us showed good internal consistency (Cronbach's α of 0.85 and 0.71, respectively). The LAEP-BG scores significantly correlated with other questionnaires such as the Quality of Life in Epilepsy Inventory—89 (QOLIE-89) and showed a good discriminative validity between groups with different levels of self-assessed AEs of AEDs. Conclusion: The Bulgarian version of the Liverpool Adverse Event Profile (LAEP) is a reliable and valid tool in assessing the patient-reported AEs of AEDs and their impact on the patient's outcome. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Epilepsy is a multifaceted chronic disorder with diverse and complex effects on the QOL of the patient [1]. High rates of AEs and intolerability of AEDs are important predictors of poor QOL in epilepsy and patients' outcome [2]. There are many studies on AEs of AEDs and instruments used to evaluate them [3–9]. According to the literature, the LAEP questionnaire is one of the standardized instruments to assess patient-reported AEs of AEDs. The LAEP is an instrument to measure the total side effects of a medication regimen and to quantify patients' perceptions of the most common negative side effects of AED treatment [3,10]. There are valid and available versions of the
⁎ Corresponding author at: University Hospital of Neurology and Psychiatry “St. Naum”, Louben Russev str., 1, 1113 Sofia, Bulgaria. Tel.: +359 2 9702216; fax: +359 2 8700036. E-mail address: [email protected] (R. Kuzmanova).
http://dx.doi.org/10.1016/j.yebeh.2014.08.124 1525-5050/© 2014 Elsevier Inc. All rights reserved.
LAEP in the English, Spanish, Chinese, Korean, and Portuguese languages [3,11–14]. Questionnaires or studies on the reliability and validity of instruments measuring AEs of AEDs in patients with epilepsy in Bulgarian language do not exist. The aim of the present study was the translation, cross-cultural adaptation, and validation of the LAEP in the Bulgarian language in order to use it in the Bulgarian-speaking population in providing a reliable instrument for the clinical monitoring of patients with epilepsy. 2. Methods The study group consisted of 131 consecutively enrolled patients out of a total of 449 screened patients from the Epilepsy Department of the University Hospital of Neurology and Psychiatry “St. Naum”, Sofia, Bulgaria. The patient selection was based on several criteria: (1) diagnosis of epilepsy according to the ILAE criteria for more than 1 year; (2) age of more than 18 years; (3) lack of cognitive impairment, tested with a Mini-
R. Kuzmanova et al. / Epilepsy & Behavior 39 (2014) 88–91
Mental State Examination score ≥ 28 when used as a screening scale, and sufficient reading ability; and (4) stable doses of antiepileptic drugs (AEDs) for at least 3 months prior to study entry. Patients with another progressive neurological or psychiatric disease or some other chronic severe physical comorbidity (diabetes, asthma, or heart, renal, or hepatic failure, etc.) on stable concomitant medication were excluded from the investigation. All subjects were volunteers and gave a signed informed consent to participate in the study, which was approved by the local Ethics Committee of Medical University — Sofia and conducted in accordance with the ethical standards of the Declaration of Helsinki. The participants were free to withdraw from the study at any time. All patients were asked to fill out two questionnaires: the LAEP-BG scale and the Bulgarian version of the QOLIE-89 questionnaire validated by Viteva et al. [15]. The Bulgarian version of the QOLIE-89 consists of 89 questions divided into seventeen domains: seizure worry, medication effects, health perceptions, health discouragement, work/driving/social function, language, attention/concentration, memory, overall QOL, emotional well-being, role limitations: emotional, role limitations: physical, social isolation, social support, energy/fatigue, physical functioning, and pain. The original LAEP scale consists of 19 questions that are presented as a checklist of symptoms experienced in the past 4 weeks, rated using Likert scale responses [16]. With the consent of the author, the original English version of the LAEP questionnaire was translated into Bulgarian by two independent medical experts with very good knowledge of English and good experience in adaptation of clinical tests. It was afterwards retranslated into English by two independent translators who were unaware of the original LAEP version. No major differences between the two translations were found. In order to identify problems in comprehension or cultural specificities, the preliminary Bulgarian version of the LAEP which was edited according to the rules of the Bulgarian language was administered to a pilot sample of ten patients with epilepsy attending the clinic. All questions were well-accepted. The patients filled in the final questionnaire in the hospital in our presence. They understood all the items and did not find any difficulty in answering the questions. After performing and evaluating the pilot study, we came to the conclusion that three of the items should be modified so that the inventory would become better for our purpose. First, we observed that the word “unsteadiness” had to be changed to “instability”. Second, the word “aggression” was replaced by “feeling of anger or aggression”. Third, “nervousness” was replaced by “nervousness and/or agitation”. The panel of the same experts who participated in the previous phase discussed that no further adaptations were required. Descriptive statistics were used for calculating the mean scores of the LAEP scale and demographic data. The score distribution of each item was evaluated for investigating the possible ceiling and floor effects (proportions of patients with the best and worst possible scores). The internal consistency of the LAEP scale was determined by estimating the Cronbach's α coefficient. In general, Cronbach's α N 0.7 (Nunnally's criterion) indicates high levels of internal consistency [17–19]. The test–retest reliability was evaluated by calculating ICCs. In general, values above 0.75 are indicative of reliability. The Mann–Whitney U-tests were used for the estimation of differences between correlation coefficients of items in Bulgarian and other language versions of the scale, where the correlation coefficients were transformed by Fisher transformation. The convergent construct validity was tested by estimating the correlation of the LAEP-BG with the QOLIE-89 and the discriminant validity by evaluating the difference between LAEP-BG scores and clinical parameters such as the type of epilepsy using Kruskal–Wallis ANOVA. The analyses were made using the computer software Statistica 8.0 for Windows (StatSoft Inc., USA).
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3. Results The average age of the patients was 40.13 ± 13.37 years, the mean duration of the disease was 15.61 ± 9.45 years, 43.5% were male, and the education level of 89% was relatively high (secondary school — 52% and university education — 37%). The patients with idiopathic epilepsy comprised 19.8% of the sample, with cryptogenic epilepsy 45.8%, and with symptomatic epilepsy 34.4%. All patients completed the LEAP questionnaire manually, and missing information on any of the items was not observed (analysis of missing data not supplied). The patients declared that all questions were clearly defined and that they had not encountered difficulties in completing the questionnaire. We used the original questionnaire with 19 items and created three subscales of items in accordance with the classification of Chen et al. [12]: “CNS dose-related side effects,” “Non CNS dose-related side effects,” and “Psychiatric side effects.” The “CNS dose-related side effects” subscale contained 10 items: unsteadiness, tiredness, headache, double/ blurred vision, difficulty in concentrating, shaky hands, dizziness, sleepiness, memory problems, and disturbed sleep (theoretical summary score range of 10–40 points). The “Non CNS dose-related side effects” subscale consisted of 5 items: hair loss, skin problems, upset stomach, trouble with mouth/gums, and weight gain (theoretical score range of 5–20 points) and “Psychiatric side effects” 4 items: restlessness, feelings of aggression, nervousness/agitation, and depression (theoretical score range of 4–16 points). The Cronbach's α of the total scale was 0.86, which indicates high levels of internal consistency. The Cronbach's α values of the three subscales were as follows: “CNS dose-related side effects” — 0.85, “Non CNS dose-related side effects” — 0.71, and “Psychiatric side effects” — 0.44. The Cronbach's α of the third subscale was b 0.7 and showed a low internal reliability of this subscale. That was the reason for creating two subscales of the LAEP-BG: the first one consisted of the “CNS dose-related side effects” and “Psychiatric side effects”, which are united and named “Neurological and psychiatric side effects” (14 items, theoretical score range of 14–56 points) and the second subscale was the “Non neurological side effects” (5 items, theoretical score range of 5–20 points). The two subscales had good internal reliability. The Cronbach's α for the “Neurological and psychiatric side effects” subscale was 0.85 and for the “Non neurological side effects” subscale 0.71. No significant differences were observed between the Cronbach's α coefficients of the total scale of LAEP-BG and original English (0.89) [3], Chinese (0.92) [12], Spanish (0.84) [11], Korean (0.9) [13], and Portuguese–Brazilian (0.9) [14] versions of the questionnaire. The range of observed scores was 19–66 (theoretical range: 19–76). Out of 131 patients, 2% had a score of 19 points and 1% had a score of 66 points. Forty-three percent had a score higher than 45 points. The results demonstrated no obvious floor and ceiling effects. The mean scores, medians, and test–retest reliability of the LAEP-BG determined with the ICCs were presented in Table 1. The ICCs, which evaluate the test–retest reliability, were higher than the recommended value of 0.75 and showed strong positive correlations between the first and second examinations, which prove the reliability of the scale (Table 1). The convergent construct validity of the LAEP-BG scores for the “Neurological and psychiatric side effects” subscale was high, which demonstrates good reliability of the results related to this category of negative effects of the disease (Table 2). The Kruskal–Wallis ANOVA with three levels (idiopathic, cryptogenic, and symptomatic types of epilepsy) showed a significant effect in relation to the type of epilepsy on the LAEP-BG total score (H(2,131) = 6.552, p b 0.05). A post hoc Mann–Whitney U-test showed a significant difference of the total LAEP-BG scores between patients with idiopathic and symptomatic types of epilepsy (p b 0.05). The results suggest that LAEP-BG score shows good discriminative validity between groups with different types of epilepsy.
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Table 1 The mean scores, medians, and test–retest reliability (ICCs) of the LAEP-BG (n = 131). Items
Median (range)
Mean (SD)
ICC
Unsteadiness Tiredness Restlessness Feelings of anger or aggression to others Nervousness and/or agitation Headache Hair loss Problems with skin (acne, rash) Double or blurred vision Upset stomach Difficulty in concentrating Trouble with mouth or gums Shaky hands Weight gain Dizziness Sleepiness Depression Memory problems Disturbed sleep Overall score Neurological and psychiatric side effects Non neurological side effects
3 (1–4) 3 (1–4) 3 (1–4) 2 (1–4) 2 (1–4) 3 (1–4) 2 (1–4) 1 (1–4) 2 (1–4) 1 (1–4) 2 (1–4) 1 (1–4) 2 (1–4) 2 (1–4) 3 (1–4) 3 (1–4) 2 (1–4) 3 (1–4) 2 (1–4) 45 (28–60) 34 (14–49) 9 (5–20)
2.47 (1.04) 2.60 (0.96) 2.49 (0.96) 1.94 (0.95) 2.32 (0.89) 2.45 (0.99) 1.93 (1.04) 1.66 (0.99) 2.1 (1.03) 1.62 (0.74) 2.37 (0.87) 1.85 (1.08) 2.34 (1.04) 2.35 (1.15) 2.47 (0.97) 2.55 (1.03) 2.02 (0.91) 2.55 (1.02) 2.15 (1.06) 47.75 (7.82) 32.82 (7.86) 9.42 (3.17)
0.96 0.94 0.95 0.93 0.93 0.95 0.90 0.79 0.91 0.97 0.89 0.79 0.83 0.77 0.94 0.94 0.97 0.93 0.93 0.96 0.93 0.91
(0.89), Spanish version (0.84), Chinese version (0.92), Korean version (0.9), and Portuguese–Brazilian version (0.9) [3,11–14]. In the LAEP-BG, the subscale “Psychiatric side effects”, created in accordance with Chen et al. [12], showed low internal consistency (Cronbach's α = 0.44). This may be partially explained by minimum cross-cultural differences. The result gave us a reason to create the two subscales: “Neurological and psychiatric side effects” consisting of 14 items and “Non CNS dose-related side effects” consisting of 5 items, which showed high internal consistency (Cronbach's α of 0.85 and 0.71, respectively). The most important finding for the Bulgarian population were the questions pertained to the neurological and psychiatric effects of AEDs, suggesting that neurotoxic symptoms are of high significance and affect the overall QOL. This result is similar to the most common reported AEs in a study of Baker et al. [10] wherein N50% of patients reported problems with attention, concentration, memory, and fatigue [7]. There are several limitations of the current study. The main limitation of our work is that the patient sample was drawn from epilepsy clinics at a university hospital and these subjects might not be representative of patients with epilepsy in the general population. An additional study limitation includes the lack of an independent control group. Adverse effects were self-reported by the patients, and their answers could be influenced by sociocultural and environmental factors.
4. Discussion 5. Conclusion The clinical monitoring of AEs of AEDs in Bulgaria is usually underperformed, and the outcome assessment in patients with epilepsy is traditionally focused on the reduction of seizures. The LAEP-BG questionnaire is the first questionnaire assessing the patient's reported AEs of AEDs in the Bulgerian language. Our results showed that the Bulgarian version of the LAEP questionnaire is well-understood, well-accepted, short and flexible, and easy for patients to answer. The demographic and clinical characteristics of the patients enrolled in this study do not differ from those used in other language versions of the scale, and the results were similar as well. The results of the present study show that the LAEP-BG questionnaire has good reliability and validity. The Cronbach's α of the total scale is 0.86 (required criteria: α ≥ 0.8) which indicates high levels of internal consistency and similarity with other language versions of the scale: original English version
The results of this study confirm the psychometric properties of the Bulgarian version of the LAEP and provide the scientific basis for the utilization of the questionnaire for assessing the self-reported AEs of AEDs and their impact on the patient's outcome. Further investigation is needed to examine the sensitivity of the LAEP-BG to clinical change, which should be of benefit to medical practice. Acknowledgment We would like to thank Prof. Baker for his permission and encouragement for validating the questionnaire. Conflict of interest The authors declare that they have no conflicts of interest and report that this is an original paper that has not been submitted elsewhere.
Table 2 Correlations between LAEP-BG scores divided into two subscales and 17 subscales of the QOLIE-89 (n = 131). QOLIE-89
Neurological and psychiatric side effects
Non neurological side effects
Health perceptions Overall quality of life Physical function Role limitations: physical Role limitations: emotional Pain Work/driving/social function Energy/fatigue Emotional well-being Attention/concentration Health discouragement Seizure worry Memory Language Medication effects Social support Social isolation Overall health
−0.461⁎⁎ −0.411⁎⁎ −0.534⁎⁎ −0.549⁎⁎ −0.437⁎⁎ −0.303⁎⁎ −0.574⁎⁎ −0.493⁎⁎ −0.521⁎⁎ −0.601⁎⁎ −0.498⁎⁎ −0.326⁎⁎ −0.491⁎⁎ −0.432⁎⁎ −0.388⁎⁎ −0.204⁎ −0.291⁎ −0.661⁎⁎
−0.214⁎ −0.265⁎⁎ −0.219⁎ NS NS NS NS NS NS NS NS NS NS NS NS NS NS NS
NS — no statistical significance. ⁎ Statistical significance of Spearman's correlation coefficient at p b 0.05. ⁎⁎ Statistical significance of Spearman's correlation coefficient at p b 0.001.
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