Efficacy of a minimal home-based psychoeducative intervention in patients with advanced COPD: A randomised controlled trial

Efficacy of a minimal home-based psychoeducative intervention in patients with advanced COPD: A randomised controlled trial

Respiratory Medicine 121 (2016) 109e116 Contents lists available at ScienceDirect Respiratory Medicine journal homepage: www.elsevier.com/locate/rme...

1MB Sizes 0 Downloads 34 Views

Respiratory Medicine 121 (2016) 109e116

Contents lists available at ScienceDirect

Respiratory Medicine journal homepage: www.elsevier.com/locate/rmed

Efficacy of a minimal home-based psychoeducative intervention in patients with advanced COPD: A randomised controlled trial D.G. Bove a, *, K. Lomborg b, c, A.K. Jensen d, e, D. Overgaard f, B.Ø. Lindhardt g, J. Midtgaard h, i a

Department of Pulmonary & Infectious Diseases, Copenhagen University Hospital, Nordsjælland, Dyrehavevej 29, 3400 Hillerød, Denmark Department of Clinical Medicine, Aarhus University, Aarhus, Denmark Department of Public Health, Section for Nursing, Aarhus University, Aarhus, Denmark d Institute of Public Health, Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark e Research Unit, Copenhagen University Hospital, Nordsjælland, Denmark f Department of Nursing, Metropolitan University College, Copenhagen, Denmark g Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark h Institute of Public Health, Section of Social Medicine, University of Copenhagen, Copenhagen, Denmark i The University Hospital Centre for Health Research, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark b c

a r t i c l e i n f o

a b s t r a c t

Article history: Received 23 June 2016 Received in revised form 1 November 2016 Accepted 3 November 2016 Available online 5 November 2016

Background: Anxiety is a common comorbidity in patients with advanced Chronic Obstructive Pulmonary Disease (COPD) with major impact on quality of life and associated with increased risk of death. The objective of this randomised controlled trial was to test the efficacy of a minimal home-based psychoeducative intervention versus usual care for reducing symptoms of anxiety in patients with advanced COPD. Methods: The trial included 66 participants with advanced COPD and symptoms of anxiety. The primary outcome was anxiety assessed by the Hospital Anxiety and Depression scale (HADS) subscale for anxiety (HADS-A). The secondary outcome was mastery assessed by the Chronic Respiratory Questionnaire (CRQ) domain of mastery (CRQ-M). Assessments were performed at baseline and one and three months postintervention. Results: The intervention group had a lower post intervention HADS-A score on average, compared with the control group (p ¼ 0.005), indicating a significant effect of the intervention. The average difference between the groups in HADS-A was 2.16 points (CI ¼ [0.62; 3.71]) at one month and 2.32 points (CI ¼ [0.74; 3.89]) at three months follow-up. The intervention group had a higher post intervention CRQ-M score on average compared with the control group (p ¼ 0.016). The average differences between the groups were 0.58 points (CI ¼ [0.09; 1.06]) after one month and 0.67 points (CI ¼ [0.18; 1.17]) after three months. Conclusions: The psychoeducative intervention provided sustainable symptom relief and improved the patients' self-management abilities. © 2016 Elsevier Ltd. All rights reserved.

Keywords: Anxiety COPD Self-management Cognitive behaviour therapy Non-pharmacological interventions

1. Introduction 1.1. Background Anxiety is a common comorbidity in patients with advanced chronic obstructive pulmonary disease (COPD) and associated with

* Corresponding author. E-mail addresses: [email protected] (D.G. Bove), [email protected] (K. Lomborg), [email protected] (A.K. Jensen), doov@ phmetropol.dk (D. Overgaard), [email protected] (B.Ø. Lindhardt), [email protected] (J. Midtgaard). http://dx.doi.org/10.1016/j.rmed.2016.11.009 0954-6111/© 2016 Elsevier Ltd. All rights reserved.

increased risk of hospital admission and death [1,2]. The prevalence of anxiety is estimated up to 74% [3e5], and patients with COPD are 10 times more likely to experience panic attacks compared with the general population [6]. In patients with advanced COPD, anxiety, and dyspnoea are described as the primary symptoms with a high impact on the patients' quality of life [2,4,7]. While the relationship between dyspnoea and anxiety in patients with advanced COPD is described in several qualitative studies [8e11] the underlying mechanisms are unclear. The evidence for pharmacological treatment of anxiety is inconclusive [12] and is further complicated by the population's age, reduced lung function, comorbidities, risk of side effects and

110

D.G. Bove et al. / Respiratory Medicine 121 (2016) 109e116

low treatment compliance. These factors warrant the development and evaluation of non-pharmacological alternatives. Cognitive behaviour therapy (CBT), including psychoeducation, is effective for reducing anxiety in adults [13e15], older individuals [16e18] and patients with COPD [19e24]. Studies have primarily included patients who were well enough to attend hospital-based sessions and/or group sessions. However, patients with advanced COPD are characterised by a high symptom burden and reduced mobility. Thus traditional hospital-based interventions may not cater to this specific group of patients with advanced disease. To address the special needs of patients with advanced COPD, we sought to develop and evaluate an intervention that would be clinically applicable and subsequently realistic to implement. Patients with advanced COPD are in the end stage of their disease although the disease trajectory is highly unpredictable and without any defined or validated predictors for death [25,26]. Inspired by a systematic review demonstrating the beneficial effects of a nurse-initiated intervention for managing breathlessness in patients with pulmonary cancer [27] and studies indicating that nurses can deliver CBT [28,29], we designed a minimal and home-based intervention reflecting the known barriers for participation in non-pharmacological interventions [30,31]. The primary objective was to test the efficacy of a minimal home-based psychoeducative intervention versus usual care for reducing symptoms of anxiety in patients with advanced COPD. The primary hypothesis was that the intervention would reduce anxiety as assessed by the Hospital and Anxiety and Depression Scale (HADS), subscale for anxiety (HADS-A) by 1.5 points from baseline to final follow-up at 3 months post-intervention in the intervention group compared with the control group. 2. Methods 2.1. Study design We performed a single-centre two-arm clinical randomised controlled trial (RCT) with one and three months of follow-up. The methods and design are described in detail in a protocol paper [32]. The trial is registered on clinical. gov.trial: NCT02366390. 2.2. Recruitment and participants Participants were recruited between February 2015 and January 2016 from the Pulmonary Outpatients Clinics at Nordsjællands Hospital, Denmark. The eligibility criteria included: COPD classified as category C or D according to the Global Initiative for Obstructive Lung Disease (GOLD) [33] and a Hospital Anxiety and Depression Scale (HADS) subscale for anxiety (HADS-A) score  8 [34]. A total of 163 patients with advanced COPD were screened for anxiety using the HADS-A. Of these, 66 patients met the inclusion criteria and agreed to participate (Fig. 1). 2.3. Intervention The theoretical foundation for the intervention was CBT and psychoeducation [35,36]. The cornerstone of the intervention is to give the patients insight into the interaction between thoughts, emotions, bodily sensations and behaviours. The purpose is to help and guide the patient to restructure unfavourable thoughts and behaviour patterns related to situations with anxiety and dyspnoea. The intervention was delivered by the primary investigator (PI) who is also a trained nurse. The intervention had a mean duration of 1-h and was performed in the participant's home with or without the presence of a spouse. For 95% of the participants the intervention was delivered within 1 week from randomisation or

otherwise within 2 weeks. The intervention consisted of several steps, which are inspired by the structure of a typical CBT session [37]. Delivery of the intervention was designed not to require specialist skills or a long course of training. After a brief introduction to the manual, the intention was, that the intervention could be performed by respiratory nurses. During the dialogue, the participants were handed two laminated cards with the cognitive model illustrated as a negative and a positive circle on the front and back of one card and two similar breathing techniques. The negative and positive circles and the two breathing techniques are illustrated in the protocol article [32]. To enhance fidelity and support for subsequent implementation, the intervention was described step by step in a manual. Two weeks after the home-based intervention the participants were contacted by telephone and offered a 20-min booster session [38]. 2.4. Usual care Participants in the intervention and control groups received usual care according to current guidelines for patients with advanced COPD, including non-pharmacological therapies such as pulmonary rehabilitation and advanced care planning [33]. 2.5. Outcomes measures The primary outcome was anxiety measured by the HADS-A. The HADS consists of 14 items divided into two subscales with seven items addressing anxiety (HADS-A) and seven addressing depression (HADS-D). Each item uses a four-point scale, allowing scores from 0 to 21 on each subscale. The secondary outcome was mastery (CRQ-M), one out of four domains on the CRQ. CRQ measures health-related quality of life (HRQoL) based on four domains: mastery (CRQ-M), emotional (CRQ-E), dyspnoea (CRQ-D), and fatigue (CRQ-F) [39e41]. The domains of mastery, emotional and fatigue are standardised, whereas the dyspnoea domain can be either individualised [42] or standardised [43,44]. In this trial we use the standardised dyspnoea domain (CRQ-SAS (CRQ-D)). Each domain is scored separately and includes 4 to 7 items. Higher scores indicate better quality of life. The minimal clinically important difference is 0.5 points for the mean domain score on the CRQ-SR [43]. Additional outcomes included depression measured by the HADS-D; HRQoL measured by CRQ-E, CRQ-D and CRQ-F; and numbers of admissions and length of stay. 2.6. Sample size The sample size calculation was based on the primary outcome HADS-A. To identify the minimal clinically important difference of 1.5 points [45] with an SD equal to 2.5 points, 22 participants were required in each group. As the population was characterised by advanced disease, we estimated that one-third of the included participants would drop out. Thus, 66 participants were required to detect a difference between the groups with a power of 80% and a 5% significance level. 2.7. Data collection Demographic data were collected by self-reporting, whereas medical data were obtained from medical records. All questionnaires (HADS and CRQ) were self-administered [42,43,46e48]. However, for 10 participants, it was necessary to collect the questionnaires at the participants' home address and/or assist in filling out the questionnaires. Sixteen participants were contacted by telephone to remind them to return the questionnaires. Several of

D.G. Bove et al. / Respiratory Medicine 121 (2016) 109e116

111

Fig. 1. CONSORT diagram of participant flow and follow-up in this trial.

these 16 participants were contacted several times. Delay in completing the questionnaires was primarily due to exacerbations and hospital admissions. Four participants from the control group had one to four weeks of delay in returning the questionnaires.

questionnaire and the entered data. Data entry errors were identified in less than 0.2%. This control was conducted by an external consultant with no connection to Nordsjællands Hospital or the trial.

2.8. Randomisation

2.10. Statistical analysis

The participants were randomised 1:1 to intervention plus usual care (intervention group) or usual care (control group). The randomisation was conducted using a system of sequentially numbered opaque sealed envelopes. The randomisation was conducted by an independent co-worker not involved in the trial.

We analysed the longitudinal outcomes by linear mixed effects regression models using R (R Core Team, 2015) and the lme4 package [49]. By virtue of the randomised design, we used the constrained longitudinal data analysis model with a random intercept on the subject level [50]. Overall tests for no treatment effect with respect to each of the longitudinal outcomes were performed using a parametric bootstrapped likelihood ratio test based on 20,000 simulations. In addition, 95% confidence intervals were calculated by a similar bootstrap procedure and the percentile method. We used an exact two-sample permutation test for the number of admissions and the

2.9. Data management Data from the questionnaires were entered into an Accessdatabase by the PI. To increase the internal validity, 40% of the entered data were assessed for concordance between the original

112

D.G. Bove et al. / Respiratory Medicine 121 (2016) 109e116

length of stay. The statistical analyses were performed blinded to the actual treatment allocation, and p-values less than 5% were considered statistically significant. 3. Results 3.1. Participants The participants' flow throughout the trial is illustrated in Fig. 1, and baseline characteristics are presented in Table 1. At baseline, no notable or clinically relevant differences were noted between the intervention and control groups in HADS-A screening score, age, sex, Forced Expiratory Volume in 1 s (FEV1), Medical Research Council (MRC) dyspnoea scale, or pulmonary rehabilitation. However, it should be noted that the prevalence of diabetes was increased in the intervention group compared with the control group. A total of 66 patients were included. Of these participants, three participants dropped out and one participant died before baseline assessment. Thus, 62 participants were included in the analysis. All patients in the intervention group (n ¼ 32) completed the full intervention including the booster session. A total of 86% of participants completed the entire follow-up. The percentage of drop outs was twice as high in the control group vs. the intervention group (18% vs. 9%). Participants who dropped out (n ¼ 9) were characterised by a higher level of anxiety when screened pre-trial (12 points vs. 11points) compared with participants who remained in the trial. No differences were found in age or grade of dyspnoea assessed by the MRC. In all, 95% of the data for the HADS and CRQ scores were available. 3.2. Treatment effect for primary and secondary outcomes Participants in the intervention group had a lower post intervention HADS-A score on average than participants in the control group (p ¼ 0.005), indicating a significant effect of the intervention. The average difference between the groups was 2.16 points (CI ¼ [0.62; 3.71]) after one month and 2.32 points (CI ¼ [0.74; 3.89]) after three months. Within groups, the difference in average scores at three months compared with baseline was 0.97 points (CI ¼ [-2.16; 0.21]) for the control group, implying a relative decrease in averages of 8.58% (CI ¼ [-1.91%; 18.85%]). In the intervention group, the average difference was 3.29 points (CI ¼ [4.41; 2.15]) resulting in a relative decrease of 29.18% (CI ¼ [19.53%; 38.68%]). Fig. 2 shows the HADS-A scores along with the group average and 95% confidence intervals. For the CRQ-M, the intervention group had a significantly higher average CRQ-M score post intervention compared with the control group (p ¼ 0.016). The average differences between the groups were 0.58 points (95% CI ¼ [0.09; 1.06]) after one month and 0.67 points (CI ¼ [0.18; 1.17]) after three months. In the intervention group, the difference in the average at three months compared with baseline was 0.86 points (CI ¼ [0.51; 1.21]) resulting in a relative increase of 25.44% (CI ¼ [14.67%; 37.21%]). In the control group, the average difference was 0.19 points (CI ¼ [-0.18; 0.56]) with a relative increase of 5.67% (CI ¼ [-5.19%; 17.04%]). The CRQ-M scores are illustrated in Fig. 3. 3.3. Treatment effect in additional outcome measures A significant difference between the groups was observed for the CRQ-E (p ¼ 0.026) post intervention. After one month, the intervention group had a higher value on average compared with the control group with a difference of 0.46 points (CI ¼ [0.01; 0.90]).

After three months, the difference increased to 0.58 points (CI ¼ [0.13; 1.03]). No significant treatment effects were observed for HADS-D (p ¼ 0.192), CRQ-D (p ¼ 0.173) or CRQ-F (p ¼ 0.157). The intervention did not have a significant effect on the number of hospital admissions or the length of stay during the three months follow-up period (p-values ¼ 0.195 and 0.300, respectively). Table 2 shows the averages at each of the time points for the control and intervention groups along with 95% confidence intervals. All values are presented as the mean point scores with 95% confidence intervals estimated from the mixed model. Follow-up I was assessed one month post-intervention, and follow-up II was assessed three months post-intervention. Difference refers to the average differences between the control and intervention groups at each of the two follow-ups. The p-value refers to the likelihood ratio test of no effect of the intervention. Three patients in the control group (Table 1) were classified as GOLD B due to a FEV1 > 50% of predicted. All statistical analyses were repeated excluding the three GOLD B patients without any influence on the results. 4. Discussion The objective of this trial was to assess the efficacy of a minimal home-based psychoeducative intervention versus usual care for patients with advanced COPD. In support of our primary and secondary hypotheses, we found that the intervention was superior to usual care in reducing anxiety and increasing mastery in patients with advanced COPD. The documented effect exceeded the threshold of the minimal clinical importance difference for both the HADS-A and the CRQ-M. This significant effect in both primary (HADS-A) and secondary outcomes (CRQ-M) is supported by a retrospective study that found a relationship between HADS-A and CRQ-M and that the CRQmastery domain could explain up to 40% of the total variance of anxiety in patients with COPD [51]. The intervention did not have any effect on the symptoms of depression, fatigue and dyspnoea. These results intuitively make sense because the focus of the psychoeducative intervention was reducing anxiety and increasing mastery of dyspnoea, and themes related to depression and fatigue were not addressed. Other studies [20,22,52], as illustrated below, have found that their intervention decreased depression, which may be explained by more intensive interventions than ours and a longer follow-up period. To the best of our knowledge, this trial is the first to exclusively test the efficacy of a minimal home-based CBT-inspired intervention on patients with advanced COPD. Three RCTs by Kunik et al. [20], Hynninen et al. [22], and Lamers et al. [52] are most comparable to our trial. Kunik et al. (2001) demonstrated that one group session of CBT decreased depression and anxiety in elderly patients with COPD. The work of Hynninen (2010) revealed that seven weeks of 2-h CBT group interventions reduced symptoms of anxiety at both two and eight months follow-up in patients with COPD. Lamers et al. (2010) demonstrated that a minimal nurse-initiated and CBT-inspired individual intervention reduced symptoms of anxiety in patients with COPD at nine months follow-up. Two out of the three studies were based on group sessions. Information regarding the severity of COPD was sparse, and none of the interventions were fully comparable to ours. However, these studies support the plausible application of our psychoeducative intervention in mediating and maintaining a long-lasting effect on anxiety in patients with advanced COPD. Our analysis did not indicate that the effect of the intervention was declining, however, we have no knowledge of whether the participants can retain the efficacy beyond the three months.

D.G. Bove et al. / Respiratory Medicine 121 (2016) 109e116

113

Table 1 Baseline characteristics of participants in the trial. Baseline characteristics

Intervention group (n ¼ 33)

Control group (n ¼ 33)

All participants (n ¼ 66)

p-value

Age, years# Sex, female * HADS-Aa screening# Body mass index# Current smoker * Alcohol consumption above recommendationsb, (n ¼ 65) * Civil and occupational status Married and/or cohabiting * Retired due to health or age * Level of education (n ¼ 65) No education * Medium academic or trade * Academic * Unemployed * Lung function Home Oxygen * FEV1% predicted# Medical Research Councils (MRC) dyspnoea scale ¥ (n ¼ 65) GOLD-classification GOLD-Bc* GOLD-C * GOLD-D * Comorbidities Cardiovascular disease * Cancer * Diabetes * Osteoporosis * Hospitalisation the previous 12 monthsd Total numbers of admissions ¥ Total numbers of admissions related to COPD ¥ Pulmonary rehabilitatione the previous 12 monthsd Not participated at all * Has participated but not completed * Has participated and completed * Is participating at present * Use of social services Help with personal care * Help to solve practical tasks * Primary nursing care *

70.06 (8.39) 22 (66.67) 11.21 (2.56) 23.76 (7.06) 10 (30.30) 7 (21.21)

70.33 (8.73) 22 (66.67) 11.03 (2.48) 23.50 (4.87) 9 (27.27) 4 (12.50)

70.20 (8.50) 44 (66.67) 11.12 (2.50) 23.63 (6.00) 19 (28.79) 11 (16.92)

0.897 1.000 0.769 0.103 1.000 0.388

14 (42.42) 32 (96.97)

16 (48.48) 33 (100.00)

30 (45.45) 65 (98.48)

0.559 1.000

14 (42.42) 17 (51.52) 2 (6.06) 1 (3.03)

23 (71.88) 9 (28.12) 0 (0.00) 0 (0.00)

37 (56.92) 26 (40.00) 2 (3.08) 1 (1.52)

0.054

7 (21.21) 33.21 (13.12) 4.00 [3.00, 5.00]

5 (15.15) 34.76 (13.48) 4.00 [4.00, 5.00]

12 (18.18) 33.98 (13.22) 4.00 [3.00, 5.00]

0.750 0.637 0.734

0 (0.00) 7 (21.21) 26 (78.79)

3 (9.09) 7 (21.21) 23 (69.70)

3 (4.55) 14 (21.21) 49 (74.24)

0.204

13 (39.39) 1 (3.03) 9 (27.27) 9 (27.27)

7 (21.21) 0 (0.00) 2 (6.06) 10 (30.30)

20 (30.30) 1 (1.52) 11 (16.67) 19 (28.79)

0.433 1.000 0.048** 1.000

1.00 [0.00, 3.00] 1.00 [0.00, 2.00]

1.00 [0.00, 2.00] 0.00 [0.00, 1.00]

1.00 [0.00, 2.75] 1.00 [0.00, 1.75]

0.230 0.134

18 (54.55) 2 (6.06) 8 (24.24) 5 (15.15)

20 (60.61) 1 (3.03) 9 (27.27) 3 (9.09)

38 (57.58) 3 (4.55) 17 (25.76) 8 (12.12)

0.802

10 (30.30) 16 (48.48) 7 (21.21)

7 (21.21) 12 (36.36) 8 (24.24)

17 (25.76) 28 (42.42) 15 (22.73)

0.573 0.455 1.000

Values are presents as * frequency (percentages), # mean (SD), ¥ median ([IQR]), **P < 0.05. a The Hospital Anxiety and Depression Score (HADS, subscale for anxiety. b The Danish Health Authority recommends no more than 7 units of alcohol per week for women and 14 for men. c The patients categorised as GOLD-B were all characterised by a high symptom burden and were evaluated by a highly experienced pulmonary consultant as high-risk patients, although they had a spirometric assessment of FEV1> 50% of predicted. d Previous 12 months refers to the time from baseline and 12 months back in time. e Pulmonary rehabilitation includes physical training combined with patient education and is administrated for 10 weeks.

Another theme for discussion is whether the effect of the psychoeducative intervention is caused by deterioration in the control group combined with a stabilisation in the intervention group, which was reported in another study testing the effectiveness of a minimal self-management intervention [53]. However, as illustrated in Figs. 2 and 3, the control group had rather stable levels of anxiety and mastery, while the intervention group's scores changed over time. This pattern strengthens our belief that the psychoeducative intervention mediates the effect in reducing anxiety and increasing mastery in patients with advanced COPD. This assumption is underpinned by a qualitative study nested in this trial exploring the patient's perspective on the psychoeducative intervention. This study found that the patients with advanced COPD experienced the psychoeducative intervention as valuable and applicable in their everyday lives for self-management of anxiety and dyspnoea (Currently undergoing review elsewhere). 4.1. Strengths, limitations and methodological considerations Strengths of our trial include the randomised controlled design, the use of reliable and valid tools (HADS and CRQ), few missing data, data control conducted by an independent consultant and

blinding of the statistician. Participant blinding was not possible. One important limitation of this trial is that we cannot be sure that all participants answered the baseline questionnaires (HADS and CRQ) before they were informed of their group allocation. Although the participants were instructed and encouraged to complete the baseline questionnaires as soon as they received them by post, at least four participants did not comply as illustrated in the flow diagram (Fig. 1). One participant died in the period between inclusion and allocation, and the baseline questionnaire was not available. Three participants had the intention to participate in the trial, but were unable to complete the baseline questionnaires due to recent or present exacerbations. The PI was first informed of this when contacting the participants to inform them of their group allocation. The participants who dropped out had a higher level of anxiety compared with participants who completed follow-up. We do not have any pre-baseline data about symptoms of depression, however, we do know that anxiety and depression are highly correlated and that depression is associated with low treatment compliance [54]. However, this finding is not considered a problem as there were no differences between the groups regarding HADS-A screening scores at baseline. In the interpretation of our results it has to be noted that the

114

D.G. Bove et al. / Respiratory Medicine 121 (2016) 109e116

Fig. 2. A ‘spaghetti plot’ illustrating the HADS-A scores along with group average and 95% confidence interval. Follow-up I was assessed one month post-intervention, and follow-up II was assessed three months post-intervention.

Fig. 3. A ‘spaghetti plot’ illustrating the CRQ-M scores along with group average and 95% confidence interval. Follow-up I was assessed one month post-intervention, and follow-up II was assessed three months post-intervention.

Table 2 Outcome scores at baseline and follow-up, and differences between the intervention and control group. Control Group Baseline

Intervention Group

Difference

pvalue

Follow-up I

Follow-up II

Baseline

Follow-up I

Follow-up II

Follow-up I

Follow-up II

HADS- 11.26 [10.29; A 12.22] CRQ-M 3.38 [3.04; 3.73]

10.40 [9.14; 11.69] 3.60 [3.17; 4.03]

10.29 [8.99; 11.60] 3.58 [3.14; 4.02]

11.26 [10.29; 12.22] 3.38 [3.04; 3.73]

2.32 [0.74; 3.89]

0.005

0.58 [0.09; 1.06]

0.67 [0.18; 1.17]

0.016

3.54 [3.27; 3.80]

3.59 [3.23; 3.95]

3.55 [3.18; 3.92]

3.54 [3.27; 3.80]

0.46 [0.01; 0.90]

0.58 [0.13; 1.03]

0.026

CRQ-D

2.96 [2.65; 3.28]

2.81 [2.42; 3.20]

2.89 [2.49; 3.29]

2.96 [2.65; 3.28]

CRQ-F

2.90 [2.64; 3.17]

3.03 [2.66; 3.41]

2.83 [2.45; 3.22]

2.90 [2.64; 3.17]

HADSD

9.34 [8.44; 10.26]

9.48 [8.28; 10.68] 9.51 [8.29; 10.74] 9.34 [8.44; 10.26]

7.97 [6.72; 9.22] 4.25 [3.82; 4.67] 4.13 [3.78; 4.48] 3.27 [2.88; 3.65] 3.32 [2.96; 3.68] 8.47 [7.31; 9.63]

2.16 [0.62; 3.71]

CRQ-E

8.24 [6.98; 9.50] 4.17 [3.75; 4.60] 4.04 [3.69; 4.40] 3.16 [2.78; 3.55] 3.15 [2.79; 3.52] 8.21 [7.04; 9.39]

0.35 [-0.09; 0.80] 0.38 [-0.07; 0.83] 0.173 0.12 [-0.36; 0.61] 0.49 [0.00; 0.98]

0.157

1.28 [-2.77; 0.23]

0.192

1.04 [-2.54; 0.46]

D.G. Bove et al. / Respiratory Medicine 121 (2016) 109e116

trial population consisted of more females than males, although equally distributed between intervention and control group. This could be random, or it could be explained by higher prevalence of anxiety among women [55]. Since we did not specify any subgroup analyses in the protocol, these are not conducted according to The International Council for Harmonisation (ICH E9) guidelines for statistical principles for clinical trials. Data on whether the participants complied with practicing breathing techniques and consulting the cards with the cognitive model would have been desirable and could have contribute to our knowledge about potential exposure response. However, this information was not assessed because the patients (n ¼ 3) who pilot tested the intervention clearly stated that it was not realistic to ask participants to keep a diary or log their level of compliance with the intervention [32]. We can discuss whether the collection of questionnaires in the participants' home can be perceived as an intervention on its own, thereby introducing a risk of bias. However, if the PI did not collect the questionnaires, data representing the group of participants most affected by their disease would have been missing, thus significantly influencing the validity. It was our intention as described in the protocol [32] to measure HRQoL with SGRQ in addition to the CRQ. However, during the data-management phase, it was noted that the SGRQ lacked significant amounts of data such that no imputation models would be feasible or credible. This incompleteness in answering the SGRQ was due to a generic misinterpretation of how the questionnaires should be completed correctly and raises the question of the validity of using SGRQ in a Danish population with advanced COPD. 5. Conclusion This trial demonstrates that a home-based psychoeducative intervention may provide immediate and sustainable symptom relief for patients with advanced COPD. The intervention was applicable and responded to the need for self-management strategies for symptom relief in this large and growing population of patients with advanced COPD. Conflict of Interest statement The authors have no conflicts of interest. Acknowledgments The authors would like to thank Malene Kronborg for performing the data control and Charlotte Bjernved Nielsen from the Research Unit at Nordsjællands Hospital, University of Copenhagen, Denmark for being responsible for the randomisation. Moreover, we owe a special thanks to all of the nurses affiliated with the Outpatient Clinic at the Department of Pulmonary Medicine at Nordsjællands Hospital, University of Copenhagen, Denmark, and to Ellen Moseholm Larsen, Andreas V. Jensen, Gertrud B. Knudsen and Pelle Trier for supporting the PI during the trial period. Finally, we owe a special warm thanks to all of the patients who made it a priority to be part of this trial. This work was financial supported by a grant from TrygFonden [109444]. The project also received funding from the Novo Nordisk Foundation [11781] and Sister Marie Dalgaard's Foundation. Appendix A. Supplementary data Supplementary data related to this article can be found at http:// dx.doi.org/10.1016/j.rmed.2016.11.009.

115

References [1] M. Divo, C. Cote, J.P. de Torres, C. Casanova, J.M. Marin, V. Pinto-Plata, J. Zulueta, C. Cabrera, J. Zagaceta, G. Hunninghake, B. Celli, BODE Collaborative Group. Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease, Am. J. Respir. Crit. Care Med. 186 (2012) 155e161. [2] M.I. Pumar, C.R. Gray, J.R. Walsh, I.A. Yang, T.A. Rolls, D.L. Ward, Anxiety and depression-Important psychological comorbidities of COPD, J. Thorac. Dis. 6 (2014) 1615e1631. [3] T.G. Willgoss, A.M. Yohannes, Anxiety disorders in patients with COPD: a systematic review, Respir. Care 58 (2013) 858e866. [4] A.M. Yohannes, G.S. Alexopoulos, Depression and anxiety in patients with COPD, Eur. Respir. Rev. 23 (2014) 345e349. [5] A.M. Yohannes, T.G. Willgoss, R.C. Baldwin, M.J. Connolly, Depression and anxiety in chronic heart failure and chronic obstructive pulmonary disease: prevalence, relevance, clinical implications and management principles, Int. J. Geriatr. Psychiatry 25 (2010) 1209e1221. [6] N. Livermore, L. Sharpe, D. McKenzie, Panic attacks and panic disorder in chronic obstructive pulmonary disease: a cognitive behavioral perspective, Respir. Med. 104 (2010) 1246e1253. [7] J.A. Cully, D.P. Graham, M.A. Stanley, C.J. Ferguson, A. Sharafkhaneh, J. Souchek, M.E. Kunik, Quality of life in patients with chronic obstructive pulmonary disease and comorbid anxiety or depression, Psychosomatics 47 (2006) 312e319. [8] S. Strang, A. Ekberg-Jansson, I. Henoch, Experience of anxiety among patients with severe COPD: a qualitative, in-depth interview study, Palliat. Support Care 12 (2014) 465e472. [9] T.G. Willgoss, A.M. Yohannes, J. Goldbart, F. Fatoye, “Everything was spiraling out of control”: experiences of anxiety in people with chronic obstructive pulmonary disease, Heart Lung 41 (2012) 562e571. [10] R.T. Disler, A. Green, T. Luckett, P.J. Newton, S. Inglis, D.C. Currow, P.M. Davidson, Experience of advanced chronic obstructive pulmonary disease: meta-synthesis of qualitative research, J. Pain Symptom Manage 48 (6) (2014 Dec) 1182e1199. [11] D. Halpin, M. Hyland, S. Blake, C. Seamark, M. Pinnuck, D. Ward, B. Whalley, C. Greaves, A. Hawkins, D. Seamark, Understanding fear and anxiety in patients at the time of an exacerbation of chronic obstructive pulmonary disease: a qualitative study, JRSM Open 6 (2015), 2054270415614543. [12] Z.A. Usmani, K.V. Carson, J.N. Cheng, A.J. Esterman, B.J. Smith, Pharmacological interventions for the treatment of anxiety disorders in chronic obstructive pulmonary disease, Cochrane Database Syst. Rev. (11) (2011). CD008483. [13] R.E. Stewart, D.L. Chambless, Cognitive-behavioral therapy for adult anxiety disorders in clinical practice: a meta-analysis of effectiveness studies, J. Consult Clin. Psychol. 77 (2009) 595e606. [14] S.G. Hofmann, J.A. Smits, Cognitive-behavioral therapy for adult anxiety disorders: a meta-analysis of randomized placebo-controlled trials, J. Clin. Psychiatry 69 (2008) 621e632. [15] A.C. Butler, J.E. Chapman, E.M. Forman, A.T. Beck, The empirical status of cognitive-behavioral therapy: a review of meta-analyses, Clin. Psychol. Rev. 26 (2006) 17e31. [16] G.J. Hendriks, R.C. Oude Voshaar, G.P. Keijsers, C.A. Hoogduin, A.J. van Balkom, Cognitive-behavioural therapy for late-life anxiety disorders: a systematic review and meta-analysis, Acta Psychiatr. Scand. 117 (2008) 403e411. [17] R.L. Gould, M.C. Coulson, R.J. Howard, Efficacy of cognitive behavioral therapy for anxiety disorders in older people: a meta-analysis and meta-regression of randomized controlled trials, J. Am. Geriatr. Soc. 60 (2012) 218e229. [18] C. Twomey, G. O'Reilly, M. Byrne, Effectiveness of cognitive behavioural therapy for anxiety and depression in primary care: a meta-analysis, Fam. Pract. 32 (2015) 3e15. [19] T.L. Barrera, K.M. Grubbs, M.E. Kunik, E.J. Teng, A review of cognitive behavioral therapy for panic disorder in patients with chronic obstructive pulmonary disease: the rationale for interoceptive exposure, J. Clin. Psychol. Med. Settings 21 (2014) 144e154. [20] M.E. Kunik, U. Braun, M.A. Stanley, K. Wristers, V. Molinari, D. Stoebner, C.A. Orengo, One session cognitive behavioural therapy for elderly patients with chronic obstructive pulmonary disease, Psychol. Med. 31 (2001) 717e723. [21] M.E. Kunik, C. Veazey, J.A. Cully, J. Souchek, D.P. Graham, D. Hopko, R. Carter, A. Sharafkhaneh, E.J. Goepfert, N. Wray, M.A. Stanley, COPD education and cognitive behavioral therapy group treatment for clinically significant symptoms of depression and anxiety in COPD patients: a randomized controlled trial, Psychol. Med. 38 (2008) 385e396. [22] M.J. Hynninen, N. Bjerke, S. Pallesen, P.S. Bakke, I.H. Nordhus, A randomized controlled trial of cognitive behavioral therapy for anxiety and depression in COPD, Respir. Med. 104 (2010) 986e994. [23] P.A. Coventry, J.L. Gellatly, Improving outcomes for COPD patients with mildto-moderate anxiety and depression: a systematic review of cognitive behavioural therapy, Br. J. Health Psychol. 13 (2008) 381e400. [24] P. Lou, P. Chen, P. Zhang, J. Yu, Y. Wang, N. Chen, L. Zhang, H. Wu, J. Zhao, A COPD health management program in a community-based primary care setting: a randomized controlled trial, Respir. Care 60 (2015) 102e112. [25] E. Fox, K. Landrum-McNiff, Z. Zhong, N.V. Dawson, A.W. Wu, J. Lynn, Evaluation of prognostic criteria for determining hospice eligibility in patients with advanced lung, heart, or liver disease. SUPPORT Investigators. Study to

116

[26] [27]

[28]

[29]

[30]

[31]

[32]

[33]

[34] [35] [36] [37] [38]

[39]

[40]

[41]

D.G. Bove et al. / Respiratory Medicine 121 (2016) 109e116 Understand Prognoses and Preferences for Outcomes and Risks of Treatments, JAMA 282 (1999) 1638e1645. A.M. Yohannes, Palliative care provision for patients with chronic obstructive pulmonary disease, Health Qual. Life Outcomes 5 (2007) 17. J.R. Rueda, I. Sola, A. Pascual, M. Subirana Casacuberta, Non-invasive interventions for improving well-being and quality of life in patients with lung cancer, Cochrane Database Syst. Rev. (9) (2011). CD004282. E.C. Montgomery, M.E. Kunik, N. Wilson, M.A. Stanley, B. Weiss, Can paraprofessionals deliver cognitive-behavioral therapy to treat anxiety and depressive symptoms? Bull. Menn. Clin. 74 (2010) 45e62. P.C. den Boer, D. Wiersma, S. Russo, R.J. van den Bosch, Paraprofessionals for anxiety and depressive disorders, Cochrane Database Syst. Rev. (2) (2005). CD004688. A. Keating, A.L. Lee, A.E. Holland, Lack of perceived benefit and inadequate transport influence uptake and completion of pulmonary rehabilitation in people with chronic obstructive pulmonary disease: a qualitative study, J. Physiother. 57 (2011) 183e190. A. Keating, A. Lee, A.E. Holland, What prevents people with chronic obstructive pulmonary disease from attending pulmonary rehabilitation? A systematic review, Chron. Respir. Dis. 8 (2011) 89e99. D.G. Bove, D. Overgaard, K. Lomborg, B.O. Lindhardt, J. Midtgaard, Efficacy of a minimal home-based psychoeducative intervention versus usual care for managing anxiety and dyspnoea in patients with severe chronic obstructive pulmonary disease: a randomised controlled trial protocol, BMJ Open 5 (2015) e008031e2015-008031. Global Initiative for Chronic Obstructive Lung Disease, Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2016. Availbe from, http://goldcopd.org/. A.S. Zigmond, R.P. Snaith, The hospital anxiety and depression scale, Acta Psychiatr. Scand. 67 (1983) 361e370. J. Walsh, Psychoeducation in Mental Health, Lyceum Books Inc, Chicago, Illinois, 2010. D.A. Clark, 1954-. Cognitive Therapy of Anxiety Disorders : Science and Practice, Guilford Press, New York, NY, 2010. D.A. Clark, 1954-, Beck AT. The Anxiety and Worry Workbook : The Cognitive Behavioral Solution, Guilford Press, New York; London, 2012. R.E. Gearing, C.S. Schwalbe, R. Lee, K.E. Hoagwood, The effectiveness of booster sessions in CBT treatment for child and adolescent mood and anxiety disorders, Depress Anxiety 30 (2013) 800e808. A.A. Reda, D. Kotz, J.W. Kocks, G. Wesseling, C.P. van Schayck, Reliability and validity of the clinical COPD questionniare and chronic respiratory questionnaire, Respir. Med. 104 (2010) 1675e1682. G.H. Guyatt, L. Berman, M. Townsend, S. Pugsley, L. Chambers, A measure of quality of life for clinical trials in chronic lung disease, Thorax 42 (1987) 773e778. H.J. Schunemann, M. Puhan, R. Goldstein, R. Jaeschke, G.H. Guyatt, Measurement properties and interpretability of the Chronic respiratory disease questionnaire (CRQ), COPD 2 (2005) 81e89.

[42] J.E. Williams, S.J. Singh, L. Sewell, G.H. Guyatt, M.D. Morgan, Development of a self-reported chronic respiratory questionnaire (CRQ-SR), Thorax 56 (2001) 954e959. [43] H.J. Schunemann, R. Goldstein, M.J. Mador, D. McKim, E. Stahl, M. Puhan, L.E. Griffith, B. Grant, P. Austin, R. Collins, G.H. Guyatt, A randomised trial to evaluate the self-administered standardised chronic respiratory questionnaire, Eur. Respir. J. 25 (2005) 31e40. [44] H.J. Schunemann, L. Griffith, R. Jaeschke, R. Goldstein, D. Stubbing, P. Austin, G.H. Guyatt, A comparison of the original chronic respiratory questionnaire with a standardized version, Chest 124 (2003) 1421e1429. [45] M.A. Puhan, M. Frey, S. Buchi, H.J. Schunemann, The minimal important difference of the hospital anxiety and depression scale in patients with chronic obstructive pulmonary disease, Health Qual. Life Outcomes 6 (2008) 46, 75256-46. [46] J.E. Williams, S.J. Singh, L. Sewell, M.D. Morgan, Health status measurement: sensitivity of the self-reported Chronic Respiratory Questionnaire (CRQ-SR) in pulmonary rehabilitation, Thorax 58 (2003) 515e518. [47] T. Phan, O. Carter, C. Adams, G. Waterer, L.P. Chung, M. Hawkins, C. Rudd, M. Ziman, N. Strobel, Discriminant validity of the Hospital Anxiety and Depression Scale, Beck Depression Inventory (II) and Beck Anxiety Inventory to confirmed clinical diagnosis of depression and anxiety in patients with chronic obstructive pulmonary disease, Chron. Respir. Dis. (2016). [48] I. Bjelland, A.A. Dahl, T.T. Haug, D. Neckelmann, The validity of the Hospital Anxiety and Depression Scale. An updated literature review, J. Psychosom. Res. 52 (2002) 69e77. [49] D. Bates, M. Maechler, B. Bolker, S. Walker, lme4: Linear Mixed-effects Models Using Eigen and S4. R Package Version 1.1-9, 2015. [50] K. Liang, S. Zeger, Longitudinal data analysis of continuous and discrete responses for pre-post designs, Indian J. Statistics 62 (2000) 134e148. [51] V.F. Parreira, R.N. Kirkwood, M. Towns, I. Aganon, L. Barrett, C. Darling, M. Lee, K. Hill, R.S. Goldstein, D. Brooks, Is there an association between symptoms of anxiety and depression and quality of life in patients with chronic obstructive pulmonary disease? Can. Respir. J. 22 (2015) 37e41. [52] F. Lamers, C.C. Jonkers, H. Bosma, G.I. Kempen, J.A. Meijer, B.W. Penninx, J.A. Knottnerus, J.T. van Eijk, A minimal psychological intervention in chronically ill elderly patients with depression: a randomized trial, Psychother. Psychosom. 79 (2010) 217e226. [53] C.C. Jonkers, F. Lamers, H. Bosma, J.F. Metsemakers, J.T. van Eijk, The effectiveness of a minimal psychological intervention on self-management beliefs and behaviors in depressed chronically ill elderly persons: a randomized trial, Int. Psychogeriatr. 24 (2012) 288e297. [54] M.R. DiMatteo, H.S. Lepper, T.W. Croghan, Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence, Arch. Intern Med. 160 (2000) 2101e2107. [55] F. Di Marco, M. Verga, M. Reggente, F. Maria Casanova, P. Santus, F. Blasi, L. Allegra, S. Centanni, Anxiety and depression in COPD patients: the roles of gender and disease severity, Respir. Med. 100 (2006) 1767e1774.