Title: Defensive coping and health-related quality of life in Chronic Kidney Disease: a cross-sectional study

Transcription

1 Author's response to reviews Title: Defensive coping and health-related quality of life in Chronic Kidney Disease: a cross-sectional study Authors: Anna Kaltsouda (akalts@cc.uoi.gr) Petros Skapinakis (p.skapinakis@gmail.com) Dimitrios Damigos (ddamigos@gmail.com) Margarita Ikonomou (ritaikonomu@yahoo.gr) Rigas Kalaitzidis (rigaska@gmail.com) Venetsanos Mavreas (vmavreas@cc.uoi.gr) Kostas C Siamopoulos (ksiamop@cc.uoi.gr) Version: 2 Date: 28 April 2011 Author's response to reviews: see over

2 Authors Response to Reviews MS: Title: Defensive coping and health-related quality of life in Chronic Kidney Disease: a cross-sectional study Authors: Anna Kaltsouda, Petros Skapinakis, Dimitrios Damigos, Margarita Ikonomou, Rigas Kalaitzidis, Venetsanos Mavreas and Kostas C Siamopoulos Version: 2 Date: 28 Apr 2011 We would like to thank the reviewers for their reports on our manuscript. Their accurate comments helped us to work on some inconsistencies or omissions that have undermined the clarity of our methods and findings. In the next paragraphs we provide details on how we have responded to their comments. Please note that changes to the manuscript have been highlighted with yellow. Reviewer 1 (Dr Santos) GENERAL COMMENTS The authors justification that perceived impairment of health-related quality of life (HRQL) has been found unrelated to CKD stage is contradicted by their own results, which show that patients undergoing dialysis (stage 5) are different from patients at stages 3/4: the former present worse physical and mental quality of life level. : We would like to thank the reviewer for pointing out this inconsistency. First, we would like to address an error in the notations on table 2 (please note that the error did not concern figures). As we can also conclude from the mean scores, significant differences exist only for PCS scores between pre-dialysis and dialysis patients. Table 2 has now been modified to correct this point. Second, we would like to note that we have re-examined our view that HRQL has been found unrelated to CKD stage. Other studies, for example in Perlman et al. (2005) (now cited), found a significant difference. When we re-consider the findings of the previously cited study (Shidler et al., 1998), we concluded that the mental health component of HRQL did not differ (we confirm this as well). However, other dimensions (e.g. objective functional ability 1

3 and subjective perception of illness effects) were worse in dialysis patients. Therefore, in the revised manuscript, we have modified the relevant sentence to: not all aspects of HRQL have been found related to CKD stage or severity MAJOR COMPULSORY REVISIONS Point 1- To describe the characteristics of the patients who were eligible but not included (at least reporting how many were in stage 3, stage 4 and under dialysis, but preferably complete demographic data). These data are essential to any comment about selection bias. In the revised version we provide all data available to us on those who refused to take part in the study. More specifically, in the results section, we have provided the following description: From the 234 patients eligible for inclusion 136 refused (81 immediately, while 55 patients although initially agreed did not appear to the scheduled appointment). Patients who refused did not differ in gender compared to patients included in the study (43% female vs 41%, p=0.54), but they tended to be older (mean age 57 vs 54, p=0.04). They were also more likely to be in pre-dialysis stages. For those who refused 88% were in pre-dialysis stages (120/136) and 12% were in ESRD (16/136), while for those who took part, the figures were 81% (79/98) and 19% (19/98) respectively (p=0.03). Please also note that our point in the Limitations section that patients on dialysis were more likely to refuse to take part in the study was incorrect (probably because we wrongly interpreted the small number of patients on dialysis as evidence of a greater refusal rate). This sentence has been modified to: it was more likely for patients who refused to be in pre-dialysis stages. Additional details on this point are provided in Authors reply on Point 2 of Major Compulsory Revisions. We agree that the number of dialysis patients included in the study was small. However, we do not quite believe that they have underrepresented the population of dialysis patients at the university of Ioannina Hospital. The actual number of eligible patients on dialysis was 35 out of 234 CKD patients in total. This small number of dialysis patients is due to the fact that there are additional dialysis centres in northwestern Greece that were not included in the study only patients attended by the Nephrology Department of the university of Ioannina were assessed. However, it is 2

4 likely that dialysis patients in our study underrepresented this population in Greece. As it is also noted in Authors reply on Point 8 of Minor Essential Revisions, appropriate revisions have been made in the Discussion and the Limitations section to give greater clarity to this issue. Point 2- To include in Limitations a more complete discussion about: (A) underrepresentation of dialysis patients (perhaps the conclusions cannot be applied to them) and (B) the possible reasons for so many refusals (so many refusals are not common in studies like this). With regard to comment (A), we would like to note that general response rate for our study was 42% (98/234) and this was 40% for pre-dialysis patients (79/199) and 54% for dialysis patients (19/35). Therefore the higher refusal rate was mainly for the predialysis patients. As it has been already addressed, appropriate revisions in the Limitations section have been made to correct our inconsistency. Regarding comment (B), the main reason of refusal was lack of time or interest in taking part in research. We believe that our patients were less motivated to participate due to the fact that several studies were taking place at that time by the nephrology department. In our opinion, it is rather unlikely that coping style was related to taking part in the study: patients did not know the specific aims of the planned research (they were informed that this would be a study on quality of life in renal disease patients). In a wider sense though, it could be assumed perhaps that refusing to participate may have resulted from a tendency to cope with the disease in a defensive way (i.e. anything that relates to the disease -even a research- is ignored in order to be kept out of conscious awareness). However, our results showed that those patients who accepted to participate did exhibit emotional defensiveness. The possible reasons for these refusals have been included in the Limitations section as indicated in comment (B). Point 3- In Methodology it is necessary to describe the method used to stratify the CKD patients: Cockcroft? MDRD? Lab clearance? CKD stages were defined by the level of estimated glomerular filtration rate in a 24- hour urine collection (egfr-24h), as a measure of overall kidney function. The 3

5 Methods section has been now revised to include the method that the nephrology department used to classify patients and the appropriate citations. MINOR ESSENTIAL REVISIONS: Point 4- In Background (first paragraph, page 3) it is necessary to include references to support that CKD patients are confronted with constant existential threat, unfamiliar stressful situations and significant alterations in everyday life. This sentence describes an anecdotal opinion about the impact that CKD might have on patients life. Since it is not based on empirical evidence, the sentence has been removed from the revised manuscript. Point 5- In Background (second paragraph, page 3), it is necessary to cite the prognostic value of HRQL: for example, whether it is able to predict mortality, adherence, etc. The paragraph has been revised to include specific findings on HRQL prognostic value as well as the relevant citations. Point 6- The term health-related quality of life is repeated so many times in the text that it would be better to use its abbreviation HRQL. We agree. Health-related quality of life has been replaced by HRQL and included in the Abbreviations section. Point 7- I suggest including in the section Background (first paragraph, page 5) the recent article Correlation between coping style and quality of life among hemodialysis patients from a low-income area in Brazil Hemodialysis International 2010; 14: , which shows that emotion-oriented coping is associated with worse physical and mental aspects of HRQL among patients undergoing hemodialysis. This suggestion is because, as stated by the authors, there are so few articles on the theme that I think a recent study cannot be missed in the references. The suggested article can also help the Discussion section. To facilitate access, I have attached the suggested article. 4

6 We would like to thank the reviewer for bringing out this recently published article that is closely related to the present study as well as for facilitating access to it. The authors have read it and included its findings in the Background and the Discussion sections of the revised manuscript. Point 8 - The authors should discuss more adequately two aspects in the Discussion section. The first is theories to explain how defensive coping can positively affect physical quality of life and negatively affect mental quality of life. This discussion will surely be expected by readers. I know the answer is out the scope of the study, but the results obligate this kind of discussion and, moreover, point to the need for future studies to answer this question. Second, and most important, although it is plausible to accept that defensive coping can positively affect physical quality of life among stage 3 (and even stage 4) patients, the statement that in the long run, defensive coping may adversely affect actual physical symptoms as well as failure to comply with medical recommendations and rehabilitation certainly applies to the underrepresented dialysis patients. It is necessary to mention that the result of defensive coping positively influencing physical quality of life may not apply to patients under dialysis (there are only 19 of them). Probably dialysis patients were the majority who refused to enroll in the study. With regard to the first comment, we would like to note that no theories have been established yet regarding the association of defensive coping and HRQL. However, additional details and relevant findings on the assumed role of defensive coping in both mental and physical health have been included in the Discussion section of the revised manuscript. Regarding the second comment, as we have already noted, the dialysis patients were not more likely to refuse. However, we agree that their actual number is small and it is likely that they do not represent the population of patients on dialysis in Greece. Therefore, in both the Discussion and the Limitations section of the revised manuscript, we have addressed the issue that, due to the small number of included dialysis patients, it is not possible to conclude whether the effects of emotional defensiveness on perceived physical health also apply to ESRD and to generalize our findings to the broader population of dialysis patients in Greece. 5

7 DISCRETIONARY REVISIONS Point 9- It would be good for the authors to firmly state that the present study makes future research necessary about the mechanisms involved in the contradictory effects that defensive coping has on the physical and mental components of quality of life among CKD patients Thank you. A greater emphasis on the need for future research is given in the Discussion and the Conclusion sections of the revised manuscript. Reviewer 2 (Dr Plantinga) MAJOR COMPULSORY REVISIONS Point 1- The authors report greater physical component scores among those with greater defensive coping after full adjustment; however, the unadjusted correlation between the two variables (Table 3) is non-significant. Is there a possibility of negative confounding here (by perhaps depression)? What adjustment(s) make this association significant? We agree with the reviewer that this is an example of negative confounding. As it can be concluded from table 3, depression is significantly correlated with both physical component scores (negatively) and defensive coping (positively). In the regression analysis, when depression is excluded from the model the beta for defensive coping is reduced to 0.19 with a p=0.23. In reply to this point we have added the following paragraph in the Discussion section: It was interesting to find that emotional defensiveness tended to predict a slightly better physical aspect of HRQL. In the unadjusted association though (see table 3), emotional defensiveness was not associated with PCS. It was depression that was significantly correlated with both PCS (negatively) and emotional defensiveness (positively). Similar observations were made for anxiety as well. In the regression analysis, when depression and anxiety were excluded from the model, the coefficient beta for emotional defensiveness was reduced (B=0.19, p=0.23). Therefore, the result of the adjusted analysis showed evidence of a negative confounding. It should be noted, however, that the adjusted association of emotional defensiveness and PCS was marginally significant 6

8 (p=0.045). Therefore, the most robust finding of the present study was the absence of a negative effect of defensive coping on physical well-being. Point 2- Time since diagnosis is likely to be a confounder, since, as the authors point out, defensive coping may only be a short-term solution. Did the authors adjust for this time? What about any measures of severity of disease and/or comorbid conditions such as diabetes or CVD? If such measures are not available, this should be a limitation. When we included time since diagnosis in the regression model, we turned up with small differences regarding the association between MCS and defensive coping style (beta = , p< when it was included, while beta = -0.68, p< when it was excluded from the model). Time since diagnosis was indeed a confounder in the mental component summary score model (beta = 6.25, p<0.001) but not in the physical component summary score model (beta = -1.95, p=0.28). Table 4 has been now revised to include adjustments for time since diagnosis. Unfortunately, no adjustments can be made for CKD severity and/or comorbid conditions, because no relevant data was collected for the study sample. We included this issue in the Limitations section of the revised manuscript. Point 3- Further, HRQOL is self-reported (SF-36), so the possibility that patients with defensive coping style report their physical health as being better than it actually is cannot be ruled out. If the authors have any objectively measured outcomes (e.g., anemia, uncontrolled blood pressure, cardiovascular events), this would strengthen the conclusion. If not, this should be addressed as a limitation. The study was design to assess perceived impairment of mental and physical wellbeing in relation with defensive coping. We agree that objectively measured outcomes of physical health would have strengthened the results but, unfortunately, we did not collect relevant data. We have addressed this point in the Limitations section of the revised manuscript. 7

9 Point 4- The breakouts of results by gender (Table 2) are not rationalized or discussed further in the manuscript. I would suggest removing these and just use gender as an adjuster. Instead, I would list scores by time since diagnosis (<3 vs. >=3 years). Table 2 has been modified to include time since diagnosis instead of gender, according to the reviewer s suggestions. Point 5- The lack of representativeness of the cohort should also be a limitation. First, nephrology clinic patients are likely different from those who are in primary care and have not been referred. Second, this is a single academic center in one limited geographic area. Third, those who refused were likely different (although the authors only report that dialysis patients were more likely to refuse). With regard to the first comment, we believe that it is unlikely for CKD patients in Greece to be in primary care, as a result of the Greek health system (they are usually under tertiary care). We agree with the second comment that study patients came from a single academic centre, which provide services to individuals from north-western Greece mainly. Therefore, we have addressed this point in the Limitations section of the revised manuscript. With regard to the third comment, please note that our statement in the Limitations section that patients on dialysis were more likely to refuse to take part in the study was incorrect. This sentence has been modified to: it was more likely for patients who refused to be slightly older as well as in predialysis stages. The possible reasons for these refusals have been also included in the revised Limitations section. In addition, patients that refused to take part in the study were compared to patients that were included with respect to their gender, age and disease stage (no additional characteristics are available to us). The Results section has been now revised to include this additional information. MINOR ESSENTIAL REVISIONS Point 6- Conclusion of the abstract is vague. Possible implications should be listed or the sentence removed. The conclusion of the abstract has been revised. 8

10 Point 7- The introduction seems very long. It could be condensed, and several of the points can be saved for the discussion. In the revised manuscript, introduction has been condensed and several issues previously addressed there have been included and further expanded in discussion. Point 8- Please provide the range of scores for the defensive coping, depression and anxiety scales, both in the Methods and table legends. Scores range from 12 to 48 for the defensive coping scale and from 0 to 4 for the depression and anxiety scales. The Methods section and the table legends have been revised to include scores range. Point 9- A comparison of characteristics of those who refused vs. those who participated would be useful in the Results. As mentioned above (Point 5, Major Compulsory Revisions), the Results section has been revised to include comparisons between patients that refused and patients that accepted to participate in the study. Point 10- Table 2: unclear comparison for p-values: between gender and disease stage? Comparisons concerned PCS and MCS for male and female patients as well as for dialysis and pre-dialysis patients. Please note, however, that Table 2 has now been revised and also includes comparisons of all subscales. Comparisons now concern the groups of dialysis vs pre-dialysis patients as well as the groups of patients diagnosed >3 years vs 3 years ago (instead of gender, as previously indicated). Point 11- Table 3: only need the diagonal and values below. Thank you! Table 3 has been revised. 9

11 Point 12- Table 4: are models adjusted for all other variables listed, as well as education, marital status, and employment? If so this should be stated. Yes, this is correct. Table 4 has been revised to make this clearer. 10