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. 2021 Feb 23;16(2):e0247336. doi: 10.1371/journal.pone.0247336

Quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia: A cross-sectional study

Ayelign Mengesha Kassie 1,*, Biruk Beletew Abate 1,#, Mesfin Wudu Kassaw 1,#, Addisu Getie 1,‡, Adam Wondmieneh 1,‡, Kindie Mekuria Tegegne 1,‡, Mohammed Ahmed 2,‡
Editor: Emilio Russo3
PMCID: PMC7901738  PMID: 33621251

Abstract

Background

Epilepsy is thought to be caused by witchcraft, evil spirit, and God’s punishment for sins in many developing countries. As a result, people with epilepsy and their families usually suffer from stigma, discrimination, depression, and other psychiatric problems. Thus, this study aimed to assess the quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia.

Methods

An institution-based cross-sectional study design was employed in this study. A simple random sampling technique was utilized. Health-related quality of life was measured based on the total score of the Quality of Life in Epilepsy Inventory (QOLIE-31) instrument. Data were entered into Epi-data 3.1 statistical package and exported to SPSS Version 20 for further analysis. Linear regression models were used to assess the relationship between quality of life and the independent variables. Statistically significant values were declared at a P-value of < 0.05.

Results

A total of 395 patients participated in the study making the response rate 98.5%. The mean age of the participants was 32.39 ±10.71 years. More than half, 199 (50.4%) of epileptic patients had an overall weighted average health related quality of life score of mean and above. Male sex (B = 4.34, 95%CI, 0.41, 8.27, P = 0.03), higher educational status (B = 7.18, 95%CI, 1.39, 13.00, P = 0.015) and age at onset of epilepsy (B = 0.237, 95%CI, 0.02, 0.45, P = 0.035) were associated with increased health related quality of life score. On the other hand, family history of epilepsy (B = -4.78, 95%CI,-9.24,-0.33, P = 0.035), uncontrolled seizure (B = -11.08, 95%CI,-15.11,-7.05, P < 0.001), more than 5 pre-treatment number of seizures (B = -4.86, 95%CI,-8.91,-0.81, P = 0.019), poor drug adherence (B = -11.65, 95%CI,-16.06,-7.23, P < 0.001), having moderate (B = -4.526, 95%CI,-8.59,-0.46, P = 0.029) to sever (B = -12.84, 95%CI,-18.30,-7.37, P < 0.001) anxiety and depression, believing that epilepsy is caused by evil spirit (B = -7.04, 95%CI,-11.46,-2.61, P = 0.002), drinking alcohol (B = -5.42, 95%CI,-10.72,-0.13, P = 0.045), and having other co-morbidities (B = -9.35, 95%CI,-14.35,-4.36, P < 0.001) were significantly negatively associated with the health related quality of life score among epileptic patients.

Conclusions

Only around half of the epileptic patients have a good health-related quality of life. In addition, multiple variables including family history, uncontrolled seizure, and poor drug adherence were associated with quality of life among epileptic patients. Hence, targeting these variables in epilepsy management is recommended.

Background

Epilepsy is a chronic and non-communicable disease of the brain. It is characterized by recurrent seizure episodes involving part of the body or the entire body. Seizure episodes are due to the release of excessive electrical discharges from a group of brain cells [1]. The seizures can present in different forms ranging from a brief lapse of attention or muscle jerks to severe and prolonged convulsions. The episodes also vary in frequency and range from less than one per year to several seizures per day. Globally, more than 50 million people are estimated to have active epilepsy, and the annual cumulative incidence rate is estimated at 67.77 per 100,000 persons [2, 3].

The risk of premature death in people with epilepsy is also up to three times higher than in the general population. Many factors including stroke, brain tumor, head injury, central nervous system infections, and genetically inherited defects are believed to be the cause of epilepsy. Different types of anti-seizure medications (ASMs) are available and are highly effective for the treatment of Epilepsy. Approximately 70% of epileptic patients are estimated to successfully respond to proper treatment with ASMs [2–4].

Despite the fact that most epileptic patients can become free from seizure attacks with the optimal use of ASMS, the treatment outcome in the majority of cases remains insufficient and many suffer from uncontrolled seizure attacks especially in low-income countries [5]. The treatment outcome of epilepsy is associated with several factors. Gender of epileptic patients, age of the patient at seizure onset, type of epileptic seizure, seizure frequency, etiology of epilepsy, and presence of co-morbidities are among these factors [6–8].

Unlike developed countries, people in developing countries especially in Africa, don’t have enough knowledge about epilepsy and is thought by many to be caused by witchcraft, evil spirit, and God’s punishment for sins and they even do not seek medical care when they are sick. As a result, epileptic patients and their families usually suffer from stigma, discrimination, and prejudice [2, 9].

It is shown that patients with epilepsy and their families most of the time prefer traditional and religious healers and in house prayers [9]. Similarly, the self-management practice of epileptic patients is very low. Concerning this, studies revealed that in developing countries, the rate of ASM therapy adherence is very poor [9, 10]. As a result, not only from recurrent seizure attacks but also patients with epilepsy are suffering from poor quality of life (QOL). QOL is a broad idea and includes the person’s physical health, mental health, level of independence, social health, personal beliefs, and their relationship to each other and with the outside environment [11].

There is a tremendous negative impact caused by the poor adherence, low self-management practice, stigma, and other co-morbid conditions on patient’s QOL, especially concerning the working conditions and personal and social relationships [12]. Therefore, psychosocial problems including anxiety, depression, social stigma, and deficiency of social backing, and unemployment can adversely affect their QOL [13–16].

Moreover, when patients took an ASM therapy for a certain time, that drug can provoke adverse effects and this can further impair their QOL [4, 17]. For these reasons, identifying predictors of reduced QOL in epileptic patients is critical to improving interventions and management strategies for epilepsy [18]. Such growing recognition of the importance of the psychosocial effects of epilepsy has led to the need to quantify QOL in affected individuals with epilepsy [16, 19].

Ethiopia shares the burden of epilepsy and over 1 million people are estimated to have active epilepsy [20]. The community’s awareness of epilepsy in Ethiopia is not different from other African countries. As a result, epilepsy is believed to be caused by witchcraft, evil spirit, and God’s punishment for sins by many [21, 22]. Consequently, patients with epilepsy in Ethiopia are suffering from physical disability, stigma, discrimination, and other psychiatric problems [10]. Despite this devastating impact, the public health community does not give epilepsy the attention it deserves. Hence, this study aimed to assess the quality of life and its associated factors among patients on anti-seizure medications therapy in North Wollo Zone public hospitals.

Methods

Study setting, design, and period

An institution-based cross-sectional was carried out in North Wollo zone public hospitals, Amhara region, Ethiopia. According to the 2007 Census conducted by the Central Statistical Agency of Ethiopia (CSA), North Wollo Zone has a total population of 1,500,303, of whom 752,895 are men and 747,408 women; with an area of 12,172.50 square kilometers [23]. The study participants were recruited from Kobo primary hospital, Lalibela primary hospital, and Woldia Comprehensive Specialized hospital. The study was conducted from February, 01 to June 30, 2020, among adult epileptic patients (age ≥ 18 years), who have been diagnosed with epilepsy, and are on at least one anti-seizure medication therapy in North Wollo zone public hospitals.

Eligibility criteria

All adult epileptic patients (age ≥ 18 years), who have been on regular follow- up for at least one year with at least one anti-seizure medications therapy were included because seizure freedom 1 year after ASM treatment is suggested as a good predictor of long-term remission [24]. However, epileptic patients who had psychiatric problems, those who are seriously ill and unresponsive for the interview, and those who had hearing problems were excluded.

Sample size determination

The sample size for this study was determined by using the single population proportion formula considering the assumptions: The proportion of epileptic patients being seizure-free, 38.6%, taken from a study in Addis Ababa (p = 0.386) because it provides the maximum sample size among the factors for quality of life [25]. Level of significance 5% (α = 0.05), Z α/2 = 1.96 and margin of error 5% (d = 0.05). The sample size was calculated as follows:

no=Z(α/2)2*p(1−p)d2

Hence, the minimum required sample size was = (1.96)2 * (0.386) (0.614)/(0.05)2 = 364. Adding a 10% non-response rate, the final sample size appeared to be 401.

Sampling technique and procedure

A simple random sampling technique was employed to select the required number of epileptic patients attending public hospitals in the North Wollo zone. First, three representative hospitals were selected randomly. Then, in these selected hospitals, the number of study participants was assigned proportionally based on the number of epileptic patients in each of those hospitals. Finally, study participants were recruited consecutively by assuming patient flow as random.

Operational definitions

Quality of life is defined as good if a participant scores mean and above the mean score of quality of life-related questions and, poor if the score is below the mean score of quality of life measuring questions.

Seizure control

The seizure status was considered to be controlled if the patient had not experienced any seizure attacks in the last one year and not-controlled if the patient experienced one or more seizure attacks in the last one-year follow-up period.

Anxiety and depression

The four-item patient health questionnaire for anxiety and depression (PHQ-4) was used to measure anxiety and depression among epileptic patients. The total score was determined by adding together the scores of each of the 4 items. Scores were rated as normal (0–2), mild (3–5), moderate (6–8), and severe (9–12) [26].

Data collection technique and quality assurance

A structured and interviewer-administered Amharic version questionnaire was used to collect data from the study participants. The questionnaire was adapted from previous comparable studies [27, 28] and was first prepared in English. Then, it was translated to Amharic and back to English for consistency of the questions. The questionnaire has three sections. The first section was about the socio-demographic characteristics of the participants. Secondly, patients, medical records were assessed to extract additional information concerning the date of initiation of ASMs, types of epilepsy, and related issues clinical issues. The third section consists of the Quality Of Life in Epilepsy (QOLIE)-31questionner which is a survey question of health-related quality of life for adults (18 years or older) with epilepsy. Health-related quality of life was measured based on the total score of QOLIE-31questionner.

A QOLIE- 31questionner consists of 31 items categorized under seven domains covering the following concepts of health: Overall Quality of Life (2 items), Medication Effects (3 items), Energy Fatigue (4 items), Seizure Worry (5 items), Emotional Well-being (5 items), Cognitive Function (6 items), and Social Function (5 items). The raw scores are rescaled from zero to 100 with higher values reflecting better QOL. Each item is scored on a scale of 0 to 100, with a score of zero representing the worst quality of life and a score of 100 representing a higher quality of life. However, possible response sets for scoring vary across questions. Examples of response sets used include (i) 0, 25, 50, 75, 100; (ii) 0, 20, 40, 60, 80, 100; and (iii) 0, 33, 67, 100 [29]. Each of the seven domains of QOL was scaled from 100%. Then, the overall weighted average quality of life score was calculated by summing the product of each of the seven domain scales times its weight and summing overall scales. Further details about the scoring of QOLIE-31questionnaire are available somewhere else [30].

Three BSc nurses were recruited for the data collection and three psychiatric nurses for supervision. A one-day training was given for the supervisors and data collectors on; the objectives of the study, the questions, and extent of explanations, the way to keep privacy and confidentiality, and other ethical issues. The supervisors coordinated the overall data collection process. A pre-test study was conducted on 5% of the sampled population by taking 23 epileptic patients at Dessie referral hospital which is not included in the study settings. The pre-test study was conducted 2 weeks before the actual data collection period. The study subjects who fulfill the inclusion criteria were selected by a simple random sampling technique. The result of the pretest was discussed and all the necessary amendments were made on the instructions, contents, order, and grammatical issues based on the pretest results. All data were checked for completeness, accuracy, clarity, and consistency by the supervisors and the investigators each night after the data were collected. Investigators and supervisors closely monitored the data collection process. Double data entry and validation were performed and data were intensively cleaned before analysis.

Data processing and analysis

Data were coded and entered into the Epi-data version 3.1statistical program and then exported to SPSS Version 20 for further analysis. Descriptive statistical methods were computed for the study variables. A simple linear regression model was used to assess the relationship between quality of life and the independent variables and then, a multiple regression analysis was run to assess the association between independent variables while controlling confounders. Linear regression model assumptions including variable measurement at the continuous level, the presence of a linear relationship between the independent and the outcome variables, absence of significant outliers, independence of observations, homogeneity of variance, normally of distribution among the errors, and absence of multicollinearity among the independent variables were assessed and all of them were fulfilled. Finally, a P-value of less than 0.05 was taken as a cut-off point to declare statistically significant associations between the independent variables and the quality of life score among the epileptic patients.

Ethical approval and consent to participant

Ethical clearance was obtained from Woldia University institutional review board with an approval number of wldu/012/2020 and support letters were written to the selected public hospitals and concerned others to obtain permission and cooperation during the data collection process. Written informed consent was obtained from each study participant before the data collection process. Confidentiality of the information was preserved and the privacy of the respondents was maintained by making the questionnaires anonymous and putting them in secured places after the data were collected.

Results

Sociodemographic and behavioral characteristics of respondents

A total of three hundred ninety-five participants volunteered and provided a complete response for the interview making the response rate 98.5%. The mean age of the participants was 32.39 with a standard deviation of 10.71 years. More than half, (58.5%) of them were females. The majority, that is 255 (64.6%) of the participants were orthodox Christianity followers and 130 (32.9%) were Muslims. Regarding marital status, 187 (47.3%) were married, 146 (37.0%) single, 49 (12.4%) divorced and the remaining 13 (3.3%) were widowed. More than half, 223 (56.5%) of the participants were rural dwellers.

Regarding education, 203 (51.4%) of the participants have no formal education, and the remaining 49.6% have completed up to higher levels of education. Occupationally, 133 (33.7%) of the participants were farmers, 52 (13.2%) government employee, 40 (10.1%) merchant, 79 (20.0%) student, and the remaining, 91(23.0%) fall in other categories (housewife, daily laborer, unemployed) (Table 1).

Table 1. Sociodemographic and behavioral characteristics of epileptic patients (n = 395).

Characteristics Category Frequency (%)
Age, years Mean±SD (32.39±10.71)
Sex Male 231(58.5)
Religion Orthodox 255(64.6)
Muslim 130(32.9)
Protestant 10(2.5)
Marital status of participants Married 187(47.3)
Single 146(37.0)
Divorced 49(12.4)
Widowed 13(3.3)
Residence Urban 172(43.5)
Educational status of Participants No education 203(51.4)
Primary 74(18.7)
Secondary 66(16.7)
Higher 52(13.2)
Occupation of Participants Gov’t employee 52(13.2)
Student 79(20.0)
Farmer 133(33.7)
Merchant 40(10.1)
Others 91(23.0)
Alcohol drinking habit Yes 82(20.8)
Smoke cigarette Yes 23(5.8)
Chew chat Yes 45(11.4)
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Clinical characteristics of study participants

Eighty-four (21.3%) of the study participants had a family history of epilepsy. Around 60 percent of the participants had a generalized type of epileptic seizure and the remaining had a focal type of seizure. Thirty-seven percent of the participants have claimed that they have lived with the disease for more than one year before seeking medical treatment. About 73.0% of the patients have attended epilepsy treatment follow up for more than 2 years. Regarding treatment regimen, around 59.0% of the patients were on polytherapy for epilepsy. In addition, only 44.8% of the patients were found to be adherent to ASMs. All patients were found to have anxiety and depression ranging from mild to severe levels. Furthermore, 55.2% of the epileptic patients had uncontrolled seizure status (Table 2).

Table 2. Clinical characteristics of epileptic patients (n = 395).

Characteristics Category Frequency (%)
Family history of epilepsy Yes 84(21.3)
Type of epileptic seizure Generalized 236(59.7)
Age of the patient at the onset of epilepsy <30 years 300(75.9)
30-45years 78(19.7)
>45 years 17(4.3)
Pre-treatment duration with epilepsy ≤ 12 month 249(63.0)
Pre-treatment number of seizures ≤ 5 seizures 125(31.6)
Duration of epilepsy treatment follow up < = 2 years 107(27.1)
Epilepsy treatment regimen Monotherapy 163(41.3)
Believe that epilepsy is caused by an evil spirit Yes 93(23.5)
Adherence to ASMs Good 177(44.8)
Level of anxiety and Mild 169(42.8)
Depression Moderate 152(38.5)
Severe 74(18.7)
Other co-morbidity Yes 73(18.5)
Seizure control status Uncontrolled 218(55.2)
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Health-related quality of life among epileptic patients

The average total quality of life score of the seven domains of health-related quality of life among epileptic patients was as follows: Seizure worry (63.43±26.56); Overall quality of life (58.48±21.22); Emotional wellbeing (62.73±18.34), Energy/fatigue (58.00±20.48), Cognitive function (73.03±23.01), Medication effects (71.49±25.62), and Social functioning (74.97±22.56). The overall weighted average health-related quality of life score was 86.54±24.31. More than half, 199 (50.4%) of epileptic patients have an overall weighted average quality of life score above or equal to the mean score level, and the remaining,196 (49.6%) had an overall weighted average quality of life score below the mean.

Factors associated with health-related quality of life

In the bivariate linear regression analysis; participants age, educational status, family history of epilepsy, epilepsy treatment follow-up duration, having an uncontrolled seizure, pre-treatment number of seizure, poor adherence to anti-seizure medications, having a severe level of anxiety and depression, poor sleep pattern, believing that epilepsy is caused by an evil spirit, drinking alcohol, cigarette smoking, chewing chat and having other co-morbidities were significantly associated with the health-related quality of life among epileptic patients.

On the multivariable linear regression analysis model, about 50.8% of the total variation in health related quality of life among epileptic patients was explained by the variables included in the model. Male sex (B = 4.34, 95%CI: 0.41, 8.27, P = 0.03), higher educational status (B = 7.18, 95%CI: 1.39, 13.00, P = 0.015), and age at onset of epilepsy (B = 0.237, 95%CI: 0.017, 0.45, P = 0.035), were associated with increased health related quality of life score among epileptic patients.

On the other hand, having family history of epilepsy (B = -4.78,95%CI: -9.24,-0.33, P = 0.035), having uncontrolled seizure (B = -11.08, 95% CI:-15.11,-7.05, P < 0.001), pre-treatment number of seizures (B = -4.86, 95%CI:-8.91,-0.81, P = 0.019), poor adherence to anti-seizure medications (B = -11.65, 95%CI: -16.06,-7.23, P < 0.001), having moderate anxiety and depression (B = -4.526, 95%CI: -8.59, -0.46, P = 0.029), having sever anxiety and depression (B = -12.84, 95CI: -18.30,-7.37, P < 0.001), believing that epilepsy is caused by evil spirit (B = -7.04, 95%CI: -11.46,-2.61, P = 0.002), drinking alcohol (B = -5.42,95%CI:-10.72,-0.13, P = 0.045), and having other co-morbidities (B = -9.35, 95%CI: -14.35,-4.36, P < 0.001) were significantly negatively associated with the health related quality of life among epileptic patients (Table 3).

Table 3. Linear regression analysis of factors for health-related quality of life in epileptic patients (n = 395).

Independent Variables Crude Beta 95% CI for Beta P-value Adjusted Beta 95% CI for Beta P-value
Age
Mean±SD (32.39±10.71) -0.29 (-0.51,-0.07) 0.011 -0.25 (-0.53,0.02) 0.072
Sex
 Male 3.55 (-1.33,8.42) 0.153 4.34 (0.41,8.27) 0.030
 Female 1
Educational status
 No education 1
 Primary 1.02 (-5.15,7.19) 0.75 2.91 (-2.23,8.06) 0.267
 Secondary 2.75 (-3.70,9.19) 0.403 3.05 (-2.60,8.69) 0.289
 Higher 5.41 (-1.70,12.51) 0.135 7.18 (1.39,13.00) 0.015
Marital status
 Married 7.16 (2.39,11.93) 0.003 7.21 (-2.99,17.42) 0.165
 Single 1.21 (-3.78,6.19) 0.635 0.81 (-9.97,11.60) 0.882
 Divorced -14.83 (-21.99–7.68) <0.001 -3.19 (-14.34,7.96) 0.574
 Widowed 1
Family history of epilepsy
 Yes -9.44 (-15.25,-3.64) 0.002 -4.78 (-9.24,-0.33) 0.035
 No 1
Age at onset of epilepsy in years (Mean±SD, 24.62±12.58) 0.15 (-0.05,0.34) 0.138 0.24 (0.02,0.46) 0.035
Treatment follow-up in years (Mean±SD, 5.20±4.20) 0-.99 (-1.56,-.43) .001 -0.12 (-0.60,0.36) 0.624
Uncontrolled seizure -20.49 (-24.89.-16.10) <0.001 -11.08 (-15.11–7.05) <0.001
Epilepsy type
 Generalized 4.03 (-0.86,8.93) 0.106 -1.62 (-5.39,2.14) 0.397
  Focal 1
Pre-treatment number of seizures
 > = 5times -7.270 (-12.40,-2.14) 0.006 -4.86 (-8.91,-0.81) 0.019
 < 5times 1
Treatment regimen
 Monotherapy 1
 Polytherapy 3.64 (-1.242,8.51) 0.144 -0.72 (-4.44,3.00) 0.703
Shortage of ASMs 0.32 (-4.68,5.32) 0.900 -2.21 (-6.07,1.65) 0.260
Adherence to ASMs
 Good 1
 Poor -25.86 (-29.97,-21.76) <0.001 -11.65 (-16.06,-7.23) <0.001
Anxiety and depression
 Mild 1
 Moderate 0.66 (-4.28,5.61) 0.792 -4.53 (-8.59,-0.46) 0.029
 Severe -25.35 (-30.99,-19.72) <0.001 -12.84 (-18.30,-7.37) <0.001
Sleep pattern
 Poor 9.66 (4.78,14.55) <0.001 2.97 -0.10,6.94) 0.142
 Good 1
Belief that epilepsy is due to an evil spirit
 Yes -16.80 (-22.23,-11.38) <0.001 -7.04 (-11.46,-2.61) 0.002
 No 1
Alcohol drinking
 No 1
 Yes -14.50 (-20.26,-8.74) <0.001 -5.42 (-10.72,-0.13) 0.045
Cigarette smoking
 No 1
 Yes -10.73 -20.96,-0.50) 0.040 5.13 (-4.37,14.63) 0.289
Chat chewing
 No
 Yes -7.96 (-15.50,-0.42) 0.039 -3.10 (-10.60,4.40) 0.417
Co-morbidity
 No
 Yes -16.31 (-22.30,-10.32) <0.001 -9.35 (-14.35–4.36) <0.001
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Model fitness: R2 = 50.8%

Discussion

In this study, around half, 49.6% of epileptic patients had poor quality of life. This finding is consistent with study findings from Jimma University (49.7%) and Addis Ababa at Amanuel specialized hospital (45.8%) [27, 28]. It is also in line with a study conducted at the University of Gondar Referral Hospital which has revealed that 44.2% of participants were found to have a poor quality of life [31]. Researchers in Italy have reported a consistent finding that 43.3% of patients had poor quality of life at a health institution study [32].

However, it is higher than a study at Ambo general hospital that 24.4% had an overall poor health-related quality of life [33]. This variation might be due to differences in the tool and operational definitions. Unlike, the current study, the previous study has used the World Health Organization Quality of Life (WHOQOL) tool for measuring the health-related quality of life among epileptic patients which is not specific for epilepsy while, the current study was conducted using the Quality of Life Inventory for Epilepsy (QOLIE-31) a specifically designed tool to measure health-related quality of life among epileptic patients [30].

Regarding the quality of life score of the seven domains of QOLIE-31, participants scored the lowest average score on the Energy/fatigue domain, and the highest score was found in the Social functioning domain. A similar study has reported a consistent finding that participants have scored the highest mean under the social functioning domain [27]. This means patients with epilepsy are having an acceptable social interaction with the community which is encouraging. However, the low score under the energy/fatigue domain is worrying because it is an indication that patients with epilepsy are suffering from tiredness, loss of energy, and related impacts on their life [33].

Regarding the factors related to the quality of life, male sex, attaining higher education, and ages at the onset of epilepsy were positively associated with quality of life among epileptic patients. Being male was associated with increased quality of life scores among epileptic patients. This finding is in line with a study in Portugal that the female gender was associated with poorer health-related in patients with refractory epilepsy [34]. A consistent finding was also reported in India that the female gender was associated with reduced quality of life among epileptic patients [35]. This might be due to the effect of hormonal changes occurring throughout a woman’s life which can influence and be influenced by seizure mechanisms and ASMs, presenting unique management challenges and this, in turn, may affect their quality of life [36]. It might be also due to a lack of social support. Unlike men, women in Ethiopia usually stay at home and work in the house and might not get sufficient social support from the community.

Having higher educational status was also associated with increased quality of life among epileptic patients. This finding is supported by studies conducted at Ambo general hospital [33], Mekelle City, Northern Ethiopia [37], Uganda [38], Kenya [39], and Iraq [40]. A consistent finding was also obtained in Indonesia that level of education was one of the positive predictors of quality of life in patients with epilepsy [41]. This could be due to the influence of education on individual perception of their disease condition and adherence to their medications. It might be also due to employment opportunities because people with higher educational status are highly likely to have different job offers and be employed by both governmental and non-governmental organizations.

As the age of onset of epilepsy increases, the quality of life of patients was also increased. This is supported by a study conducted in Malaysia [42]. A person with epilepsy diagnosed in childhood would likely have many schooling hours disrupted if the frequency of seizures were uncontrolled and this could also lead to low educational achievement, and thus a lower employability potential. Furthermore, the seizure itself may cause accidents and injuries thus preventing sufferers from driving and depriving many types of employment opportunities, this, in turn, has the potential of negatively affecting the quality of life of epileptic patients [43].

On the other hand, the present study revealed that having a family history of epilepsy, having an uncontrolled seizure, pre-treatment number of seizures, poor adherence to ASMs, believing that epilepsy is caused by an evil spirit, drinking alcohol, having moderate to severe anxiety and depression and having other co-morbidities were negative predictors of quality of life among epileptic patients.

Family history of epilepsy was associated with decreased quality of life among epileptic patients. This is supported by a study conducted among children and adolescents in Iran which has reported that a family history of epilepsy was significantly associated with health-related quality of life [44]. A consistent finding was also found in a study conducted among patients with refractory mesial temporal lobe epilepsy in Brazil [45]. This might be due to the influence of perceived stigma among epileptic patients. Because, when there is epilepsy in a family, the community might have stigmatizing behavior towards the family as epilepsy is believed to be caused by God’s curse, evil spirit, and witchcraft by many [46]. Furthermore, people might see epilepsy as a contagious disease, which in turn may result in a lack of social support, stigma, and discrimination among patients [47, 48].

The present study showed that pre-treatment number of seizures more than five times, and having uncontrolled seizures have negatively affected the quality of life of epileptic patients. The finding is supported by studies conducted in Ethiopia [37, 49], Uganda [38], and Iraq [40]. The possible reason could be because of seizure frequency, a known risk factor that can cause excessive fear, inability to work, stigmatization, diminished hope, and future life, impairment in social functions, and psychological impairments [42]. Individuals with frequent epileptic seizures will always be in discomfort because; they do not know when the next seizure might happen. As a result, they might take extra-care and impose self-restrictions from driving, cooking, and doing risky jobs to avoid having seizure episodes at inappropriate times, places, or social events [50, 51]. This in turn has a tremendous potential of compromising the quality of life of epileptic patients.

Having moderate to severe anxiety and depression, and other co-morbidities resulted in decreased quality of life in epileptic patients. This finding is supported by studies conducted in China [52], Ethiopia [31, 49], and Kenya [53]. This could be due to the effect of these problems on quality of life, particularly, in the domains of lethargy/fatigue, and emotional well-being [53]. It might be also due to pill burden and drug interactions resulting from concomitant treatments [54]. Believing that epilepsy is caused by evil spirits negatively affects the quality of life of epileptic patients. This could be due to the influence of cultural beliefs on attitudes and uncaring actions of the community towards patients with epilepsy [55] which in turn can result in high rates of low self-esteem in patients with epilepsy, thus adversely affecting the quality of life [56].

Furthermore, drinking alcohol was associated with a reduced quality of life among epileptic patients. This might be due to the effect of alcohol on the frequency of seizure attacks resulting in a possible negative effect on the quality of life. Because, alcohol is a known precipitating factor for seizure disorders [57, 58]. Besides, alcohol consumers might have alcohol-drug interactions and this might further result in recurrent seizure attacks among patients [59, 60]. This might be also due to poor adherence to medications as a result of prolonged treatment for epilepsy with ASMs. Poor drug adherence is a known factor that was found to have a negative association with health quality of life among epileptic patients in this and many other studies, and, might result in a poor quality of life if patients are non-adherent to ASMs.

Conclusion

In this study, only around half of the epileptic patients had a good quality of life. Furthermore, multiple variables including family history, uncontrolled seizure, poor adherence, and having anxiety and depression were associated with health-related quality of life among epileptic patients. Hence, targeting these variables in epilepsy management is essential. Moreover, early recognition of adherence issues and detecting and managing co-morbid conditions by the clinician can have a great impact on controlling seizure attacks and increasing the quality of life of epileptic patients.

Supporting information

S1 Data. SPSS data file.

(SAV)

Click here for additional data file. (405KB, sav)

Acknowledgments

The authors would like to express our gratitude to the data collectors and supervisors for their great contribution. Our deepest gratitude also goes to those who participated in this study.

Abbreviations

ASM

Anti-Seizure Medications

PWE

People Living With Epilepsy

SPSS

Software Package of Social Science

WHO

World Health Organization

Data Availability

All relevant data are within the paper and its Supporting Information files.

Funding Statement

The study was funded by Woldia University. Amount received =21,642 Ethiopian Birr.

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Decision Letter 0

Emilio Russo

17 Dec 2020

PONE-D-20-34326

Quality of life and its associated factors among epileptic patients attending public hospitals in north Wollo Zone, northeast Ethiopia: Across-sectional study

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Reviewer #1: Based on my review results the manuscript is partly technically sound, and do the data support the conclusions because few informations on result and conclusion were has discrpancy with the data put on the table. The authers used appropriat model for thire problem however I have not get any information how they check the model fitness. Regards to data availablity the authors have not made all data underlying the findings in their manuscript fully available. eg SPSS data. Some edditorial issues are avaialable related to English language.

Reviewer #2: The manuscript describes quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo zone, Ethiopia. There are several major points that need to be addressed and revised by the authors first before accepting the manuscript for publication. Moreover, line spacing and line numbering were not applied as per the PLoS one guideline. Hence it is difficult to evaluate the manuscript point by point. The manuscript has several grammar and punctuation errors that need extensive English language revision.

Title

Make space “a/cross-sectional”

Abstract

The conclusion you made is just a summary of the result. Need revision

Introduction

Several studies have been conducted in Ethiopia including in Jima University, in Gondar, Ambo….What is new in your study? and please clearly state in the introduction section.

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Why at least one AED use and 1 year since diagnosis were considered as eligibility criteria?

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“…three hundred ninety five (395)…” no need to repeat the same information

” ….Christianity followers followed by 130 (32.9%).” It is an incomplete statement and revise it.

How did you collet seizure type? (did you use medical chart review)?

The proportion of medication adherence is not included in the result section

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Reviewer #1: Yes: Agumas Fentahun Ayalew, Master Of Public Health in Epidemiology, Salale University, Health Science College, Department of Public Health, Fitche, Ethiopia

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PLoS One. 2021 Feb 23;16(2):e0247336. doi: 10.1371/journal.pone.0247336.r002

Author response to Decision Letter 0

23 Dec 2020

To: Plose One Editorial Team

Subject: Submitting a revised research manuscript for publication

Dear Sir /Madam

Greetings,

I am Ayelign Mengesha from Woldia University, Ethiopia. I hereby submit a revised manuscript entitled “Quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia: a cross-sectional study” to be published at Plose One.

First of all I would like to express my deepest gratitude on behalf of the authors for the very detail, genuine and constructive comments raised by the reviewer/s and, or the editor which I believe has improved the manuscript tremendously. We believe that we have addressed the points raised in the review process properly. The modifications and, or corrections made during the revision are clarified point by point below.

Yours sincerely,

On behalf of the authors

General corrections/modifications:

Table has been included for clinical variables.

Grammatical, spelling and punctuation mark issues are corrected with grammerly proof reading tool and with intense revision by the authors.

Other corrections/modifications are described in detail under point by point responses below.

Editor comments

Comment: Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.

Author response: The manuscript has been revised intensively in line with the journal’s requirements.

Comment: Please include in your Methods section (or in Supplementary Information files) the participating hospitals/institutions.

Author response: Revised in methods section paragraph 1 as follows: The study participants were recruited from Kobo primary hospital, Lalibela primary hospital, and from Woldia Comprehensive Specialized hospital. The study was conducted from February, 01 to June 30, 2020.

Comment: We suggest you thoroughly copyedit your manuscript for language usage, spelling, and grammar.

Author response: Grammatical, spelling and punctuation mark issues are corrected with grammerly online proofreading and with intense revision by the authors.

Comment: Please provide further clarification whether IRB approval was obtained from all participating hospitals prior to data collection.

Author response: Ethical approval and consent to participant: Ethical clearance was obtained from Woldia University institutional review board and support letters were written to the selected public hospitals and concerned others to obtain permission and cooperation during the data collection process. Methods section, last paragraph. However, ethical approval from hospitals was not applicable because the hospitals but, permission to conduct the study in the hospitals was obtained.

Comment: Please ensure that you include a title page within your main document. We do appreciate that you have a title page document uploaded as a separate file, however, as per our author guidelines (http://journals.plos.org/plosone/s/submission-guidelines#loc-title-page) we do require this to be part of the manuscript file itself and not uploaded separately. Could you therefore please include the title page into the beginning of your manuscript file itself, listing all authors and affiliations?

Author response: I apologize for failing to include the title page in the main document. I have included the title page with author details within the main document.

Comment: Thank you for stating the following in the Funding Section of your manuscript: "The study was funded by Woldia University". We note that you have provided funding information that is not currently declared in your Funding Statement. However, funding information should not appear in the Acknowledgments section or other areas of your manuscript. We will only publish funding information present in the Funding Statement section of the online submission form. Please remove any funding-related text from the manuscript and let us know how you would like to update your Funding Statement. Currently, your Funding Statement reads as follows: "Data supporting the conclusions of this article are included within the article and its supporting files". Please include your amended statements within your cover letter; we will change the online submission form on your behalf.

Author response: Funding should be written in the following ways: The study was funded by Woldia University. Amount received =21,642 Ethiopian Birr.

Comment: The manuscript describes quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo zone, Ethiopia. There are several major points that need to be addressed and revised by the authors first before accepting the manuscript for publication. Moreover, line spacing and line numbering were not applied as per the PLoS one guideline. Hence it is difficult to evaluate the manuscript point by point. The manuscript has several grammar and punctuation errors that need extensive English language revision.

Author response: Dear Agimas Fentahun Ayalew, I thank you very much for your genuine and constructive comments: I have revised the manuscript intensively. Grammatical and punctuation mark issues corrected with grammerly proof editing and with intense revision by the authors.

Title

Comment: Make space “a/cross-sectional”

Author response: Space added, a cross-sectional study

Abstract

Comment: The conclusion you made is just a summary of the result. Need revision

Author response: It has been revised with adjusted beta and confidence interval in the result section and conclusion. Page 2.

Introduction

Comment: Several studies have been conducted in Ethiopia including in Jima University, in Gondar, Ambo….What is new in your study? and please clearly state in the introduction section.

Author response: Thank you for your view, as you might have seen in the result section, several variables were included in this study. In addition, many of the studies have used WHO quality of life tool to assess quality of life among epileptic patients which is general and is not specific in terms of content. But, in this study, we have used the Quality of life in epilepsy inventory; QOLIE-31 questionnaire which is designed to measure quality of life among epileptic patients. The study area is also quite different compared with other studies. It is not sufficiently addressed with health care services.

Method

Comment: Why at least one AED use and 1 year since diagnosis were considered as eligibility criteria?

Author response: The study participants were included if they were on treatment with AEDs because adherence was one of the variables which was included in this study. But, if a patient who has stopped taking drugs because he has been seizure free and was advised to stop taking the drugs by physicians comes to the hospitals for consultation and counseling, he will not be included. At least one AED was mentioned here because it is recommended to start treatment with one AED, and if patients fail to respond for that drug, then they will take additional drugs accordingly.

At least one year was treatment was also another criterion to be included because seizure freedom 1 year after AED treatment is suggested as a good predictor of long-term remission (reference 24). If patients gain long term remission (being seizure free 2-3 years), then it is possible to discontinue the drugs and follow the patient for possible seizure relapse. Some other studies have used the same criteria. Page 5.

Comment: How simple random sampling technique was carried? How do you access the sampling frame?

Author response: Revised, patient flow was assumed as random and it is written as follows: finally, study participants were recruited consecutively by assuming patient flow as random. Page 5 last paragraph.

Comment: You have stated “…questionnaire was adapted from previous comparable studies.” please cite some of them.

Author response: Citations added. It is revised as follows: The questionnaire was adapted from previous comparable studies (27, 28). The questionnaire was first prepared in English. Then, it was translated to Amharic and back to English for consistency of the questions. Page 6.

Comment: Who collects the actual data (their qualification…)?

Author response: It revised as follows: To ensure the quality of data, three BSc nurses were recruited for the data collection. In addition, three psychiatric nurses were also recruited for supervision. Page 7.

Result section

Comment: “…three hundred ninety five (395)…” no need to repeat the same information

Author response: Removed

Comment:” ….Christianity followers followed by 130 (32.9%).” It is an incomplete statement and revise it.

Author response: Thank you; it is revised as: Majority, that is 255 (64.6%) of the participants were orthodox Christianity followers and 130 (32.9%) were Muslims. Page 8.

Comment: How did you collet seizure type? (did you use medical chart review)?

Author response: Yes, chart review was done for some variables. It is revised as follows: the questionnaire has three sections. The first section was about socio demographic characteristics of the participants. Secondly, patients, medical records were assessed to extract additional information concerning to the date of initiation of AEDs, types of epilepsy and related issues clinical issues. The third section consists the Quality Of Life in Epilepsy (QOLIE)-31questionner which is a survey question of health-related quality of life for adults (18 years or older) with epilepsy. Page 6-7.

Comment: The proportion of medication adherence is not included in the result section.

Author response: Included in table 2.

Abstract: Male sex, higher educational status, and age at onset of epilepsy having family history of epilepsy treatment follow-up duration, having uncontrolled seizure, pre-treatment number of seizures, poor adherence to anti-epileptic drugs, having moderate anxiety and depression, having sever anxiety and depression, believing that epilepsy is caused by evil spirit, drinking alcohol, and having other co morbidities were negative predictors; write these factors with OR & CI.

Author response: Revised as follows: Male sex (B = 4.34, 0.41, 8.27), higher educational status (B = 7.18, 1.39, 13.00) and age at onset of epilepsy (B = 0.237, 0.017, 0.45) were associated with increased health related quality of life score. On the other hand, family history of epilepsy (B = -4.78, -9.24,-0.33), uncontrolled seizure (B = -11.08, -15.11,-7.05), more than 5 pre-treatment number of seizures (B = -4.86, -8.91,-0.81), poor drug adherence (B = -11.65, -16.06,-7.23), having moderate (B = -4.526, -8.59, -0.46) to sever (B = -12.84, -18.30,-7.37) anxiety and depression, believing that epilepsy is caused by evil spirit (B = -7.04, -11.46,-2.61), drinking alcohol (B = -5.42, -10.72,-0.13), and having other co-morbidities (B = -9.35,-14.35,-4.36) were significantly negatively associated with the health related quality of life score among epileptic patients. Page 2.

Conclusion: Almost half of the epileptic patients have an overall weighted average health related quality of life score below the mean score level. This conclusion is opposite of your statement written on your result???? ‘’ More than half, 199 (50.4%) of epileptic patients have overall weighted average health related quality of life score above or equal to the mean score level’’.

Author response: Thank you, it is revised as: Only around half of the epileptic patients had good quality of life. In addition, multiple variables including family history, uncontrolled seizure, poor adherence, and having anxiety and depression were associated with health related quality of life among epileptic patients. Hence, targeting these variables in epilepsy management is recommended. Page 2.

Comment: The largest ethnic group in north Wollo is the Amhara (99.38%) and all other ethnic groups made up 0.62% of the population. Amharic is spoken as a first language by 99.28% of the population and the remaining 0.72% spoke other primary languages. 82.74% of the populations are Ethiopian Orthodox Christianity followers, and 17.08% are Muslims. I think this paragraph is un necessary for your study, instead add the number of epileptic or study populations in the study area and try to relate your study population with the study area!!!!

Author response: Revised as follows in Study setting, design, and period section. An institution-based cross-sectional was carried out in North Wollo zone public hospitals, Amhara region, Ethiopia. According to the 2007 Census conducted by the Central Statistical Agency of Ethiopia (CSA), North Wollo Zone has a total population of 1,500,303, of whom 752,895 are men and 747,408 women; with an area of 12,172.50 square kilometers (23). The study participants were recruited from Kobo primary hospital, Lalibela primary hospital, and Woldia Comprehensive Specialized hospital. The study was conducted from February, 01 to June 30, 2020. Methods section, first paragraph.

Comment: What is the deference between source population and study population on your study? If not you can use one of the two.

Author response: Revised: Source population: Adult patients (age ≥ 18 years), who have been diagnosed with epilepsy, and are on at least one anti-epileptic drug therapy in north Wollo zone public hospitals. Study population: Adult patients (age ≥ 18 years), who have been diagnosed with epilepsy and have been on regular follow- up for at least one year with at least one anti-epileptic drug therapy in selected public hospitals. Therefore, the epileptic patients who have been on regular follow in selected public hospitals were the study populations because; they are the actual population where samples were taken. Page, 5.

Comment: You have two objectives magnitude of quality of life and factors associated with it, but you didn’t show any thing about you calculates sample size for the second objective. How could you see this? Since it can be affect the validity of result.

Author response: Thank you for the comment. It is revised as follows: The sample size for this study was determined by using the single population proportion formula considering the assumptions: The proportion of epileptic patients being seizure free, 38.6%, taken from a study in Addis Ababa (p = 0.386) because it provides the maximum sample size among the factors for quality of life (25). Level of significance 5% (α = 0.05), Z α/2 =1.96 and margin of error 5% (d = 0.05). The sample size was calculated as follows:

no = Z (α/2)2*p (1-p)

d2

Hence, the minimum required sample size was = (1.96)2*(0.386) (0.614)/ (0.05)2= 364. Adding 10% non-response rate, the final sample size appeared to be 401. However, in a paper to be published, we have thought that putting all the procedures of sample size calculation might not be important. Page, 5.

Comment: Finally which method of simple random sampling technique method do you used please try to clarify it!

Author response: Revised: Finally, study participants were recruited consecutively by assuming patient flow as random. Page, 5-6.

Comment: Result: Two hundred seventy four (60.4%). This information varies from the data on the table.

Author response: It is corrected that more than half, (58.5%) of them were females. Page, 8.

Comment: Pre-treatment duration with epilepsy “≤ 12 month”: This is out of your inclusion criteria. See your inclusion criteria.

Author response: In our eligibility criteria: All adult epileptic patients (age ≥ 18 years), who have been on regular follow- up for at least one year with at least one anti-epileptic drug therapy were included.. However, the duration that patients live with epilepsy before seeking treatment is not an exclusion criterion. Before seeking treatment, patients might have lived with epilepsy for one year and above and this is not our inclusion criteria. What we excluded was patients who have less than one year treatments follow up period because, seizure freedom 1 year after AED treatment is suggested as a good predictor of long-term remission (reference 24). Page 4.

Comment: Your tool contains socio demographic characteristics of the participants. The second section covers a data extraction checklist on seizure control status and related issues. The third section consists the Quality Of Life in Epilepsy (QOLIE)-31questionner which is a survey question of health-related quality of life for adults (18 years or older) with epilepsy. Health related quality of life was measured based on total score of QOLIE-31questionner. A QOLIE- 31questionner consists 31 items categorized under seven domains covering the following concepts of health: Overall Quality of Life (2 items), Medication Effects (3 items), Energy Fatigue (4 items), Seizure Worry (5 items), Emotional Well-being (5 items), Cognitive Function (6 items), and Social Function (5 items). Therefor where is your table which is containing most parts of your study variables……..? I have got only socio-demographic and logistic regression table only.

Author response: Thank you for your insightful comment. We have seen that only sociodemographic and some clinical variables were included in table one. Therefore, another table is included as table 2 to show the necessary Variables separately from table one. Page. 10.

Comment: What is the difference between overall quality of life and overall weighted average quality of life? Which is better for your study? Try to make clear is for readers and use your best one!

Author response: Each of the seven domains of QOL was scaled from 100%. Quality of life was one of the seven domains and it was measured by using 2 questions. And then, the overall weighted average quality of life score was calculated by summing the product of each of the seven domain scales times its weight and summing overall scales. Further details about the scoring of QOLIE-31 are available somewhere else (Reference 30; Quality of Life in Epilepsy inventory, QOLlE-31 (Version 1.0) Scoring Manual: Available at: https://www.rand.org/content/dam/rand/www/external/health/surveys_tools/qolie/qolie31_scoring.pdf, (Accessed on September 3, 2019).

Comment: “about 50.8% of the total variation in health related quality of life among epileptic patients was explained by the variables included in the model”. Is it appropriate model? Where is the other 49.2%. When we say it is a good model?

Author response: R-squared that is the explained variation / Total variation always ranges between 0 and 100%. 0% indicates that the model explains none of the variability of the response data around its mean. On the other hand, 100% indicates that the model explains all the variability of the response data around its mean. In general, it is considered that the higher the R-squared, the better the model fits the data. However, it is not always true. In our study, the value of R-square is >50 percent and it is a good model as far as it explains more than 50% of the variations.

Comment: Linear regression analysis of factors for health related quality of life in epileptic patients. I didn’t get any information on the methodology part about linear regression model assumption were full filed or not!

Author response: Linear regression model assumptions, that that is variable measurement at the continuous level, the presence of linear relationship between the independent and the outcome variables, absence of significant outliers, independence of observations, homogeneity of variance, normally of distribution among the errors and absence of multicollinearity among the independent variables were assessed and all of them were fulfilled. Page, 7-8.

Comment: Author’s Contribution: AMK participates in all steps of the study from its commencement to writing. BBA, MWK, AD, AW, and MA have participated in reviewing the paper, analysis and interpretation of the data. All authors have read and approved the submission of the final manuscript. Include all this authors on the cover page!

Author response: I apologize for failing to do this; all have been included in the first page.

Decision Letter 1

Emilio Russo

26 Jan 2021

PONE-D-20-34326R1

Quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia: a cross-sectional study

PLOS ONE

Dear Dr. Kassie,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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furthermore, improve the language used.

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We look forward to receiving your revised manuscript.

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Emilio Russo

Academic Editor

PLOS ONE

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Comments to the Author

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Reviewer #1: All comments have been addressed

Reviewer #3: (No Response)

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Reviewer #1: Yes

Reviewer #3: Partly

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Reviewer #1: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #3: Yes

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6. Review Comments to the Author

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Reviewer #1: This paper has a potential to be accepted, the authors have adequately addressed my comments raised in a previous round of review and I feel that this manuscript is now acceptable for publication since the manuscript technically sound, and do the data support the conclusions

Reviewer #3: Authors deeply improved the manuscript in the revised version, addressing previous comments. However, further modifications are needed before publication:

1 - Abstract: please report data in results as: (B= ..., 95%CI ...; p ...)

2 - Epilepsy nomenclature should be allineate with new ILAE definition (2018), for instance: partial seizures should be referred as focal seizures (in the text as well in the tables), etc.

3 - Background, pag 3, lines 1-6: please provide a more detailed/technical characterization of epilepsy.

4 - Please change Antiepileptic drugs (AEDs) in "antiseizure medications (ASMs) throughout the manuscript.

5 - "with an area of 12,172.50 square kilometers" not relevant information.

6 - Please combine study setting, Source population and study population paragraphs, avoiding redundant data.

7 -Please combine and synthetize "data collection technique and tools" and "Data quality assurance" paragraphs for better clearness and readability.

8 - "Ethical approval" - the local Ethical Committee has provided an approvation number/protocol? If so, please state it. Please remove sentences as: "All participants were asked for their 12 willingness to participate in the study and were told that it will not have any risk on them", these information are implicit in the informed consent.

9 - Tables 1and 2 - please report frequency and percentage in the same column as: frequency (percentage), for instance sex male 231 (58.5). For dichotomic data (e.g. sex, alcohol drinking habit, smoke, chew chat) please report in the table one of the variable, eg. smoke 23 (5.8). remove blankets for age data.

10- table 1 and 2 - please remove "2020" and "North Wollo Zone public hospitals 2020" from the titles.

11 - Please provide Nagelkerke R2 for multivariate regression analysis.

12 - recheck the manuscript for typos.

**********

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Reviewer #1: Yes: Agumas Fentahun Ayalew

Reviewer #3: No

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PLoS One. 2021 Feb 23;16(2):e0247336. doi: 10.1371/journal.pone.0247336.r004

Author response to Decision Letter 1

3 Feb 2021

To: Plose One Editorial Team

Subject: Submitting a revised research manuscript for publication

Dear Sir /Madam

Greetings,

I am Ayelign Mengesha from Woldia University, Ethiopia. I hereby submit a revised manuscript entitled “Quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia: a cross-sectional study” to be published at Plose One.

First of all I would like to express my deepest gratitude on behalf of the authors for the very detail, genuine and constructive comments raised by the reviewer/s and, or the editor which I believe has improved the manuscript tremendously. We believe that we have addressed the points raised in the review process properly. The modifications and, or corrections made during the revision are clarified point by point below.

Yours sincerely,

On behalf of the authors

General corrections/modifications:

Grammatical, spelling and punctuation mark issues are corrected with grammerly proof reading tool and with intense revision by the authors.

The other corrections/modifications are described in detail under point by point responses below.

General comments: Authors deeply improved the manuscript in the revised version, addressing previous comments. However, further modifications are needed before publication:

Author response: I thank you very much on behalf of the co-authors for your genuine and constructive comments. We have revised the manuscript intensively based on the comments provided. I particularly would like to thank you for the updated information on the nomenclature’s of epilepsy/seizure disorders.

Comment1: - Abstract: please report data in results as: (B= ..., 95%CI ...; p ...)

Author response: Incorporated as suggested.

Comment 2 - Epilepsy nomenclature should be allineate with new ILAE definition (2018), for instance: partial seizures should be referred as focal seizures (in the text as well in the tables), etc.

Author response: Revised accordingly.

Comment 3 - Background, pag 3, lines 1-6: please provide a more detailed/technical characterization of epilepsy.

Author response:

It is revised as follows. Epilepsy is a chronic and non-communicable disease of the brain. It is characterized by recurrent seizure episodes involving part of the body or the entire body. Seizure episodes are due to the release of excessive electrical discharges from a group of brain cells (1). The seizures can present in different forms ranging from a brief lapse of attention or muscle jerks to severe and prolonged convulsions. The episode also varies in frequency, ranging from less than one per year to several seizures per day. Globally, more than 50 million people are estimated to have active epilepsy and the annual cumulative incidence rate estimated at 67.77 per 100,000 persons.

Comment 4 - Please change Antiepileptic drugs (AEDs) in "antiseizure medications (ASMs) throughout the manuscript.

Author response: Replaced/changed throughout the manuscript.

Comment 5 - "with an area of 12,172.50 square kilometers" not relevant information.

Author response: The sample was taken based on the number and/or patient flow in the study area. So, it is fair to say that the sample can be representative of the patients who were attending the hospitals at the time of the study. But, it does not mean it is representative of the population of north Wollo zone.

Comment 6 - Please combine study setting, Source population and study population paragraphs, avoiding redundant data.

Author response: They are combined.

Comment 7 -Please combine and synthetize "data collection technique and tools" and "Data quality assurance" paragraphs for better clearness and readability.

Author response: They are combined.

Comment 8 - "Ethical approval" - the local Ethical Committee has provided an approbation number/protocol? If so, please state it. Please remove sentences as: "All participants were asked for their 12 willingness to participate in the study and were told that it will not have any risk on them", these information are implicit in the informed consent.

It is re-written is follows: Ethical clearance was obtained from Woldia University institutional review board with an approval number of wldu/012/2020 and support letters were written to the selected public hospitals and concerned others to obtain permission and cooperation during the data collection process. Written informed consent was obtained from each study participant before the data collection process. Confidentiality of the information was preserved and the privacy of the respondents was maintained by making the questionnaires anonymous and putting them in secured places after the data were collected.

Author response: The section "All participants were asked for their 12 willingness to participate in the study and were told that it will not have any risk on them" is removed.

Comment 9 - Tables 1and 2 - please report frequency and percentage in the same column as: frequency (percentage), for instance sex male 231 (58.5). For dichotomic data (e.g. sex, alcohol drinking habit, smoke, chew chat) please report in the table one of the variable, eg. smoke 23 (5.8). remove blankets for age data.

Author response: Revised as suggested.

Comment 10- table 1 and 2 - please remove "2020" and "North Wollo Zone public hospitals 2020" from the titles.

Author response: removed

Comment 11 - Please provide Nagelkerke R2 for multivariate regression analysis.

Author response: Revised as follows: under table 3, Model fitness: (R2) = 50.8% and in text above table 3.

Comment 12 - recheck the manuscript for typos.

Author response: Revised with co-authors and grammerly proof editing tool. Thank you very much.

Decision Letter 2

Emilio Russo

5 Feb 2021

Quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia: a cross-sectional study

PONE-D-20-34326R2

Dear Dr. Kassie,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Emilio Russo

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

Emilio Russo

12 Feb 2021

PONE-D-20-34326R2

Quality of life and its associated factors among epileptic patients attending public hospitals in North Wollo Zone, Northeast Ethiopia: a cross-sectional study

Dear Dr. Kassie:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Prof Emilio Russo

Academic Editor

PLOS ONE

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