Telemedical care improves quality of life in patients with schizophrenia and bipolar disorder. Results of a randomized controlled trial

Background: Schizophrenia and bipolar disorder are serious psychiatric disorders with a high disease burden, a high number of years of life lived with disability and a high risk for relapses and re-hospitalizations. Besides, both diseases are often accompanied with a reduced quality of life. A low level of quality of life is one predictor for relapses. This study examines whether a telemedical care program can improve quality of life. Methods: Post stationary telemedical care of patients with severe psychiatric disorders” (Tecla) is a prospective controlled randomized intervention trial to implement and evaluate a telemedical care concept for patients with schizophrenia and bipolar disorder. Participants were randomized to an intervention or a control group. The intervention group received telemedical care including regular, individualized telephone calls and SMS-messages. The quality of life was measured with the German version of the WHOQOL-BREF. Effects of telemedicine on quality of life after 6 months were analyzed using t-tests to compare the intervention with the control group. Participants also evaluated the telemedical care program based on a short standardized interview. Results: 118 participants were recruited, thereof 57.6 % men (n = 68). Participants were on average 43 years old (SD) 13). Linear mixed model revealed that aliation to patient group (0 = CG, 1 = IG), gender (0 = female, 1 = male), increasing social support and higher GAF-level are positive signicant inuence factors for the WHOQOL total quality of life, physical, psychological, environmental and global domain. An increasing education often showed signicantly decreasing quality of life values. Age as an inuencing factor, showed different results on the sum score and the individual domains. Conclusion: The Tecla telemedical care concept has improved the quality of life in patients with severe psychiatric disorders. It provides for a low-threshold and well suitable component in psychiatric treatment.


Introduction
Mental disorders have a high disease burden and the number of days with limitations is 3 times higher in a icted patients than for healthy people [1]. The course of mental diseases is often chronic [2].
Schizophrenia and bipolar disorder are among the most serious psychiatric disorders. Schizophrenia is one of the ten diseases with the highest number of years of life lived with disability (YLD) [3]. Relapses and re-hospitalization are frequent in patients with schizophrenia and bipolar disorder [4,5]. Both diseases are often accompanied with a distinct impairment of social and professional life management and hence result in a lasting reduced quality of life [3,[6][7][8]. The World Health Organization Quality of Life (WHOQOL) Group de ned quality of life as the "individuals' perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns." [9]. All aspects of life, which means physical, social, environmental and psychological aspects, affect one's wellbeing and satisfaction [6].
Schizophrenia and bipolar disorder patients show similar levels of quality of life [6]. A low level of quality of life is a predictor for relapses [10]. Akvardar et al. showed that the improvement of quality of life is one important part in treating psychiatric disorders [7]. Hence, quality of life is an important factor and must be a target for gaining a good or at least stable state of mental health [7,11].
Telemedicine has the potential to improve the health care situation for patients within the mental health spectrum. Positive effects were shown on patients with anxiety and depression [12] and on medication adherence in patients with schizophrenia and bipolar disorder [13].
This paper reports results regarding quality of life from a prospective controlled randomized intervention trial called "Post stationary telemedical care of patients with severe psychiatric disorders" (Tecla). Tecla's objective was the implementation and evaluation of a telemedical care concept for patients with schizophrenia, schizoaffective disorder and bipolar disorder. It addressed different problematic issues in treatment and every-day-life-management [14]. Primary outcome was medication adherence, which was positively in uenced by the telemedical care concept [13]. This article aims to investigate the effects of the telemedical care concept on the quality of life of patients with schizophrenia, schizoaffective disorder and bipolar disorder. The hypothesis is that the participants of the intervention group, which received additional telemedical care, had better levels of quality of life compared to participants of a control group, which received usual care six months after baseline.

Materials And Methods
Patient sample and data Data were retrieved from the prospective controlled randomized intervention trial Tecla. Inclusion criteria of Tecla were a medical diagnosis of any form of schizophrenia (ICD-10 F20), schizoaffective disorders (ICD-10 F25), or bipolar disorders (ICD-10 F31), and age ≥ 18 years. The diagnoses were extracted from the patient les. Exclusion criteria were prior scheduled inpatient treatments within the next six months and lacking reachability by cell phone. The participants were recruited shortly before their discharge from day-care hospitals or open or locked inpatient wards from three psychiatric departments in Western-Pomerania, a Federal State in the very northeast of Germany.
Tecla has been approved by the Ethics Committee of the University Medicine Greifswald (BB 122/14) and was registered at the German Clinical Trials Register (date 2015\05\21, DRKS00008548). A comprehensive description of the study protocol for the Tecla study was published by Stentzel et al. [14].

Randomization
The participants were randomized to the intervention or control group after the baseline assessment. A blinded scientist, who was neither involved in the recruitment nor in the baseline assessment, performed the allocation to the groups using a random allocation (block randomization). The listing of the two groups was unregularly. The participants were chronically signed to the next entry in the randomization list.

Telemedical intervention
Participants were individually randomized to intervention group and control group. Both groups received care as usual in the outpatients facilities (outpatient psychiatric / psychotherapeutic practices or psychiatric institutional outpatients' departments). The intervention group received regular telephone calls every two weeks and in addition standardized as well as individualized text messages every week. An example for such an individualized text message is given in Figure 1. Quali ed nurses who are specialized in telemedical care conducted the regular telephone calls. The nurses are embedded in regular meetings within one of the psychiatric institutional outpatients' department and day-care hospital. They were trained in the documentation system and join appropriate psychiatric/psychotherapeutic education programs. The telemedical conversation was conducted on the basis of eCRFs in a computer-aided documentation system in accordance with the current standards for data security and data privacy [15,16]. The standardized conversation contained a structured standardized and an individualized part. The structured standardized part of the telephone calls included suicidal tendencies, changes in the medication regime, medication adherence and medication side effects (study protocol published elsewhere [13]). The individualized part addressed selected topics of everyday life that the respective participant evaluated as important for himself and his condition. The weekly text messages refer to actual and relevant events and themes in the daily life of the participants.

WHOQOL-BREF
The quality of life was measured with WHOQOL-BREF, the short version of the subjective instrument World Health Organization Quality of Life, which is designed for generic use [9,17]. It assesses the quality of life from a subjective perspective [7]. The short version WHOQOL-BREF has 26 items. Answers are given on 1-to-5-point Likert scales. Summing all 26 items gives total quality of life, ranging from 26 to 130 [18]. The higher the score the better the quality of life of the patient [17]. WHOQOL assesses different aspects of life that are relevant for quality of life [9]. The WHOQOL-BREF bases on four domains [9,17] and one global value for general quality of life: Physical domain: pain, energy, sleep, mobility, activities, medication, work.
Social relationships domain: personal relationships, social support, sex.
Environment domain: safety and security, home environment, nance, health/social care, information, leisure, physical environment, transport.
Global value: overall quality of life, general health.
The German version was used, which shows good internal consistence (Cronbachs α > 0.7 for all domains) for the overall population as well as for patients with mental disorders [19].

Social support
Social support was assessed using the measure F-SozU (Social support, short form with 14 items) [20]. The authors de ned social support as the result of cognitive-emotional processing and assessment of current and past social interactions. The concept is based on cognitive approaches and assesses the subjective conviction to get support from the subject's social network if necessary. This 14-item short form is appropriate for the assessment of a more generally perceived social support [20]. The statements refer to the elds of emotional support (to be liked and accepted by others, to share feelings, to experience participation), to provide practical assistance (practical help in everyday problems, for example to borrow things, getting practical advice, getting help with challenging tasks) and social integration (belonging to a circle of friends, doing joint ventures, knowing people with similar interests) and are assessed using a 5 category Likert-scale from "does not apply" (scored 1) to "applies exactly" (scored 5) [20,21].

Global assessment of functioning (GAF)
The Global Assessment of Functioning (GAF) is an overall measure of how patients are doing from positive mental health up to severe psychopathology [22]. It is known, that functioning is low in people with current mental health disorders, so functioning can be used as an expression of the severity of illness [23]. The GAF-questionnaire measures the degree of mental illness by rating psychological, social and occupational functioning [22] on an ordinal scale from 1 to 100 [24]. The scale is divided into 10point intervals. The lowest interval (score 1 to 10) represents severe illness, the highest interval (score 91 to 100) represents the healthiest condition [21,22].
Participants' evaluation of the telemedical care program Participants of the intervention group were asked to evaluate the telemedical care at the end of their study participation by answering the questions shown in Table 1. The analyses were conducted with the intention-to-treat approach. For randomized clinical trials with missing data the multiple imputation procedure is a valid method to handle missing data [25] and to minimize possible biases [26]. However, a required condition for multiple imputation is, that missing data are distributed completely at random (MCAR) or at random (MAR), whereas the method is less appropriate for data missing not at random (MNAR) [27]. After thorough inspection, we appraised the missing data as MAR. The proportions of missing values ranged from 11 -17 % (WHOQOL-variables 12 %). Hence multiple imputation was proceeded. To be able to reproduce the results, each time the analysis is performed the random seed value was speci ed [25].

Results
118 participants were recruited (see CONSORT ow diagram in Figure 2), thereof 57.6 % men (n = 68). Participants were on average 43 years old (standard deviation (SD) 13). Baseline characteristics are shown in Table 2. Except for education, there was no signi cant difference between the intervention and control group at baseline. Participants in the intervention group had a better education than participants in the control group. 104 diagnoses of schizophrenia and schizoaffective disorder (ICD-10 F2x.) and 48 bipolar disorder-diagnoses (ICD-10 F3x.) were found. 21 patients had two to three diagnoses. Further details are documented in table 1 the supplement. 90 participants remained in the study until the sixmonth follow-up. Of these, 79 participants completed the WHOQOL-BREF. Results of the linear mixed model regressions are shown in Table 3. With respect to the study group a liation the intervention group has signi cantly better values in quality of life in the total quality of life, in all WHOQOL-domains except for social relationships and the global value. That is to say that the values of the intervention group were signi cantly lower for the social relationships domain. To control for the observed differences at baseline, the level of education (0 < 10 years, 1 = 10 years, 2 > 10 years) was included in the model. The results show a very heterogeneous picture. The WHOQOL total quality of life, psychological and social relationships domains and the global values signi cantly decreases with increasing education. The physical health domain increases with increasing education, but not signi cant. In contrast, increasing education increases the environment domain signi cantly.
Regarding the in uence of social support on quality of life, it was observed for all domains, the total quality of life and the global value that the values increase signi cantly with increasing social support.
With increasing level of the Global Assessment of functioning as a measure for the impairment of the participants, the WHOQOL total quality of life and all of the four domains and the global value increased signi cantly. The increasing ranges from 0.1 -0.5 points though.
The results of the evaluation of the telemedical program by participants of the intervention-group are shown in Figure 3. Participants perceived the telemedical care mostly as moderately to very helpful (97.5 %, Figure 3A). A majority would like to continue the telemedical care (73.2 %, Figure 3B). A minority can even imagine, that the tele medical care can make contacts to doctors or psychologists less necessary or perhaps can partly replace them (34.2 %, Figure 3C).

Discussion
Quality of life is a major treatment goal for patients with psychiatric disorders [7,11,29]. As a secondary outcome, it was proved that a low-threshold telemedical care program containing regular telephone calls and SMS-messages was able to improve quality of life compared to a control group in almost all of the WHOQOL aspects. An exception was the social relationships domain. The intervention group showed lower values than the control group. This was signi cant, but close to the signi cance level of alpha 0.05. The improvement of the other domains and the WHOQOL total quality of life ranged between 2 to 4.1 points, which is moderate but clearly signi cant. The ndings are in line with another study that also investigated a mobile health (mHealth) approach. Ben-Zeev (et. al) compared the mHealth intervention FOCUS with a widely used group self-management intervention called WRAP [30]. As one of the secondary outcomes quality of life was investigated. The FOCUS participants showed signi cant improvements between baseline and the six months follow up. Even though the FOCUS intervention substantially differs slightly from Tecla, the mode of administration via information and communication technologies is similar. The general feasibility, acceptance and e ciency of electronic Health (eHealth) and mHealth interventions for people with serious mental illnesses is proven by several other studies [31][32][33].
As in uencing factors age, gender, the education level, social support and the global functioning level (GAF) were revealed. Age is known to be signi cantly related Quality of lives in patients with schizophrenia [34]. Although age was occasionally signi cant, the estimates are very low and are all close to zero. Compared to all factors gender (being male) showed the strongest in uence with ranges between 2 to 10.3. The results regarding age and male gender are corresponding with other studies [29].
Where education showed signi cant in uence, the observed estimates were moderate. Some authors regard the relationship between socio-demographic factors and quality of life as controversial, weak, or non-existent [35,36], but some reported signi cant associations [37,38]. Our results vary and do not clearly support either view. Social support has a known positive in uence on quality of life [36,39,40]. This was also signi cantly veri ed in our results. The improvement amounted moderate 0.1 to 0.8 points though. To consider also the by the disease caused disability of the subjects the GAF was included in the model. Corresponding to other studies [36,38,41], higher GAF levels showed signi cant better quality of life levels for all domains and the WHOQOL total quality of life. Similarly here, too, the estimates increased by merely moderate values (from 0.1 to 0.5 points).
However, the WHOQOL was proven as an adequate tool for assessing quality of life in different cultures and population groups [42,43]. Therefore, in this study we have adopted a generic tool [6], that can be broadly applied for assessing quality of life in different cultures and population groups [44,45]. The WHOQOL-BREF is less affected by disease-related factors [17] and has been applied in patients with schizophrenia with good reliability and validity [36,45], even in psychotic stages, on medication and in patients with relatively low education level [7]. Kim et al. compared patients' assessments of their own quality of life with WHOQOL-BREF with assessments of proxies (such as family members, caregivers) and found a moderate to good accordance between both assessments of the patients' quality of life [8].
Even though schizophrenia and bipolar disorder are different diseases, there are similarities between them like the extent of quality of life. Both diseases showed similar scores for the WHOQOL-BREF domains in previous studies [11,46]. In this study, the baseline characteristics showed no differences between the diagnostic groups (see Table 2). Hence, we analyzed both diseases together.
A strength of this study is the usual care setting with only little inclusion and exclusion criteria. Consequently, the results are likely to be transferable to a large part of the patient group and daily regular medical care. In this regular care setting, the study was conducted with a pragmatic RCT-design. To fortify the validity, a multiple imputation was performed.
The baseline assessment showed a signi cant difference between the two groups with respect to the level of education. Participants in the intervention group had a higher level of education compared to participants in the control group. A blinded scientist performed the allocation to the groups using a random allocation (block randomization) after the baseline assessment. However, the baseline characteristics showed similar values for all WHOQOL-domains for both groups (see Table 2). In fact, the intervention group had even slightly lower WHOQOL total score values. The intervention was largely standardized. Furthermore, the loss to follow-up was identical in both groups (see Figure 2). Therefore, a systematic bias seems unlikely. The proportion of loss to follow-up at the six-month-follow-up was 24 % in the invention group and 23 % in the control group. Due to the size of the dropout rates, there might be an attrition bias [47,48], but threshold levels for acceptable dropout-levels are not determined in guidelines yet [48]. Furthermore, distinct patient clienteles might require different levels. Because of the almost identical rates and because of the di cult patient clientele, we deem that potentially bias might be low. Besides, the loss to follow-up is similar to other reported dropout rates in the regarded patient groups [45]. To consider this fact, education was included in the model to control for it.
Diagnoses were extracted from the patients' les from the three recruiting psychiatric departments. In several cases, a clear diagnosis has not yet been made by the treating physicians. Therefore sometimes several diagnoses were applied here.
The duration of the illness is considered as important factor in the literature [35]. In the Tecla study, it was gathered from the patients records by date of rst diagnosis. The date was more often not available than available so that it was not possible to include the duration of the illness in to the model.
Medication and its side effects could possibly effect patients' quality of life [11] and would have been informative, but these aspects were not included here. However, it is a relevant question. Hence, the in uence of medication on various data collected within the Tecla study, including the quality of life aspect, is currently being evaluated.

Conclusion
Every aspect that can help to stabilize the patient and avoid hospitalization should be considered during treatment. The telemedical intervention shown here is a low-threshold care concept that has the potential to improve the care situation of patients with severe psychiatric diseases. Schulze