Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD cohort study patients.

BACKGROUND: Little is known about the impact of ostomy formation in inflammatory bowel disease patients on course of disease, psychological well-being, quality of life and working capacity.
METHODS: We analyzed patients over a follow-up of up to 16 years in the Swiss inflammatory bowel disease cohort study (SIBDCS) with prospective data collection. We compared Ulcerative colitis and Crohn's disease patients with and without ostomy as well as permanent and closed stoma formation before and after surgery, investigating disease activity, psychological wellbeing and working capacity in a case-control design.
RESULTS: Of 3825 SIBDCS patients, 176 with ostomy were included in the study and matched with 176 patients without ostomy using propensity score, equaling 352 patients for the analysis. As expected, we observed a lower mean and maximal disease activity in patients after stoma surgery compared with control patients without stoma. Overall, psychological wellbeing in patients with stomas vs. controls as well as patients with permanent vs. closed stoma was similar in terms of disease-specific quality of life (total score of the Inflammatory Bowel Disease Quality of Life questionnaire), psychological distress (total score of the Hospital Anxiety and Depression Scale), and stress at work (effort-reward-imbalance ratio), with the exception of a higher Posttraumatic Diagnostic Scale total score in patient with vs. without stoma. Compared to IBD patients without stoma, the adverse impact on working capacity in overall stoma IBD patients appeared to be modest. However we observe a significantly higher reduction in working capacity in permanent vs. closed stoma in CD but not UC patients.
CONCLUSION: As to be expected, IBD patients may benefit from closed and permanent stoma application. Stoma surgery appears to only modestly impact working capacity. Importantly, stoma surgery was not associated with adverse psychological outcomes, with comparable psychological well-being regardless of presence and type of stoma.

Introduction

The etiology of Inflammatory Bowel Disease (IBD) consisting of Crohn’s Disease (CD) and Ulcerative Colitis (UC) [1] is incompletely understood and the global burden is high. It is estimated that approximately 3.1 Million Americans [2] and 2.5 Million Europeans suffer from IBD [3]. Numerous pathogenetic factors are involved in these complex chronic immune-mediated diseases, including genetic predisposition, epithelial barrier effects, environmental factors and a dysregulated immune response [4]. Overall around 50% of IBD patients will need surgery during their lifetime [5]. Mostly it is necessary for difficult-to-treat IBD patients refractory to a variety of biological (i.e. all monoclonal antibodies; biologics) and non-biological (i.e. immunomodulators, corticosteroids, mesalamine, calcineurin-inhibitors, small molecules) agents, or due to complications, such as toxic megacolon, perforation, hemorrhage or peritonitis [6]. Surgical treatment encompass a wide variety of options from strictureplasty, segmental colonic, small bowel or ileo-cecal resection to complete proctocolectomy.

Complete proctocolectomy representing the standard procedure for refractory UC, nowadays in the vast majority of cases performed in a three-step (less frequently two-step) procedure, therefore encompassing closed stoma for a period of several months [7,8] with multiple anastomosis possibilities, latter being the current method of choice [9]. In UC, the risk of colectomy was shown to be 4.1%, 6.4% and 14.4% after 5, 10 and 20 years respectively with a decreasing trend according to a recent investigation in Switzerland [10] with comparable results in North-American studies [11,12]. In refractory UC the most frequent surgical procedures are ileal pouch anastomosis (IPAA) and proctocolectomy with ileostomy [13]. However, also in CD and despite advances in anastomosis techniques stoma rates are still considerable with around 1.51–1.9 stomas per 100 person years with permanent stoma formation at a stable level in recent years [14,15].

Studies have shown conflicting data on quality of life in patients after ostomy [16-19]. Moreover, stoma patients with CD have been found to display high rates of anxiety and depression without receiving sufficient psychological support [20] and stoma formation was identified as a risk factor for the development of these problems in IBD patients in general [21]. Moreover not only ostomy formation has been identified as a risk factor for post-traumatic stress symptoms but also surgery, hospitalizations, and disease severity in general as well with medical procedures, surgery being two of the main five factors identified by an American, qualitative study [22]. Additionally, studies have indicated CD-induced posttraumatic stress worsening the disease course [23] and a negative effect on work ability of IBD patients [24,25]; yet further research is needed to determine the impact of stoma surgery.

Therefore, we aimed to investigate in a case control study design whether there are differences in the course of the disease, clinical symptoms, medication use, psychological well-being, quality of life and work ability in IBD patients with vs. without ostomy as well as pre vs. post relocation surgery in those stoma patients with later closed ostomy formation.

Methods and material

Patient data and study design

All patients participating in the Swiss IBD Cohort Study (SIBDCS) with history of stoma surgery were eligible to be analyzed in our study. More details on the goals, structure and methodology of this multicenter prospective observational population-based cohort study also with regards to the validated outcome scores included in the inclusion/annual follow-up questionnaires for physicians and patients have been described elsewhere [26].

We conducted a multi-center, case-control study including patients diagnosed with either CD or UC that participated in the Swiss IBD cohort study with prospective and standardized data collection since 2005. Three groups of patients were defined and compared using Wilcoxon- and Chi-Square-Test. The first group consisted of patients who received a permanent stoma, the second group included patients whose stoma has been closed and the third group comprised of matched patients according to diagnosis, age, gender, disease duration and disease severitiy, extraintestinal manifestations (EIM) such as peripheral arthritis/artralgia, uveitis/iritis, pyoderma gangrenosum, erythema nodosum, aphthous oral ulcers, ankylosing spondylitis, sacroiliitis, and primary sclerosing cholangitis as well as a composite of typical complications associated with IBD (including gallstone formation, anemia (not due to drug adverse events), deep venous thrombosis, colorectal cancer, colonic dysplasia, pulmonary embolism, intestinal lymphoma, malabsorption syndrome, massive hemorrhage, growth failure, osteopenia/osteoporosis, perforation/peritonitis and nephrolithiasis), therapies and family history but no stoma surgery in a 1:1 ratio as a control group. Only patients undergoing construction (and removal in closed stoma group) during the prospective follow-up time in the SIBDCS were considered in our analysis. Patients with stoma surgery prior to inclusion in the SIBDCS were excluded. Patients were eligible if they had completed a minimum of one annually follow-up questionnaire for medical, psychological and work related data before, one whilst stoma in situ as well as after bowel reconnecting surgery in patients with surgical removal of stoma. Patients undergoing Ileal Pouch Anal Anastomosis (IPAA) prior to the first follow-up visit were also included. For the comparison between the control group and the stoma group, stoma had to be in place at the time of the comparison and at least three follow-ups had to be completed at year 1, 3 and 5. Disease severity was quantified using Crohn’s Disease Activity Index (CDAI) [27] for CD and Modified Truelove and Witts Activity Index (MTWAI) [28] for UC. CDAI and MTWAI were measured when the patients were included in the study as well as during annual follow up. The term severe disease was defined for CD and UC patients reaching the individual maximum value of the respective index. In the standardized SIBDCS follow-up no assessment of a modified CDAI specifically for CD patients with a stoma is designated, such as for instance a the modified score proposed by Ishida et al. which does not include liquid or soft stools often difficult to assess in patients after ostomy [29]. However, as CDAI is the most frequently used score in clinical trials [30] and has been used to assess disease reoccurrence also in other instances with surgically altered stool frequency including after ileocolic resection [31,32], we considered it to be the most feasible tool to measure disease activity after ostomy. The IBD Quality of Life questionnaire (IBDQ) [33], the Hospital Anxiety and Depression Scale (HADS) [34], the Posttraumatic Diagnostic Scale (PDS) [35] and the effort-reward-imbalance ratio [36] were used to asses psychological wellbeing. The IBDQ is a standardized questionnaire assessing quality of life specifically in IBD patients based on their symptoms with a higher score demonstrating a lower disease related quality of life or an insufficient disease control. The HADS is a validated psychometric instrument with 14 items to measure anxiety and depression with a higher total score indicating a greater level of psychological distress in the previous 7 days. The PDS measures the intensity of 17 symptoms of posttraumatic stress in the previous months according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) [37],as previously outlined [23]. Individual items of the PDS were anchored to the experience of IBD as the defining traumatic event. The PDS avoidance score assesses the need to avoid stimuli associated with the traumatic event. The PDS re-experiencing score measures for example nightmares or the feeling the trauma is happening again. A higher score indicates more recollections of the traumatic event. The PDS hyperarousal score measures for instance startle reactions. The effort-reward-imbalance ratio is an index of effort spent and the resulting reward obtained at work based on Siegrist’s Effort-Reward Imbalance model [38]. A higher effort-reward-imbalance ratio has been associated with an increased risk of various health and psychological problems [39].

Statistical analysis

Chi-square-Test [40] and Wilcoxon-Test [41] were used to compare patients with closed stoma to patients with permanent stoma. The same analyses were used for the comparison between stoma patients and patients without ostomy. In order to remove bias due to confounding variables in this observational study we used propensity score matching to select all subjects in the control group. The following information was included to match the control group and the ostomy group: diagnosis, age, gender, disease duration, occurrence of complication, prior intestinal surgery or EIM, therapy with 5-ASA, antibiotics, immuno-modulators, biologics or steroids, nonsteroidal anti-inflammatory drugs (NSAID) intake, disease activity index, family history of IBD, occurrence of “other medical history” (coeliac disease, Tuberculosis (TBC), organ transplantation or psoriasis). A p-value below 0.05 was considered significant.

Ethical approval

The SIBDCS has been approved by the Ethics Committee (BASEC Number 2018–02068). Patients gave a written informed consent before participating in the cohort study agreeing to data collection and research analysis. Moreover, the current study has been reviewed and accepted by the scientific board of SIBDCS.

Results

Patient characteristics

Amongst 3825 SIBDCS patients, 176 matched the inclusion criteria including stoma creation surgery during prospective SIBDCS follow-up and thus could be analyzed and matched to 176 SIBDCS patients without ostomy formation (54% and 46% with CD and UC, respectively), equaling a total of 352 patients analyzed. In 111 patients ostomy was permanent whereas in 65 a subsequent surgery for ostomy closure was performed. CD patients were diagnosed later after first IBD-associated symptoms than UC patients with a median disease duration of 14.8 years in CD and 8.4 years in UC respectively. The fraction of patients experiencing EIM was evenly distributed. Regarding medical therapy more immune modulators and biologics were used in CD patients with stoma. In the stoma group no significant differences could be seen in the variables at baseline when comparing permanent to closed stoma. (Table 1).

Table 1

Patient characteristics in different groups.

	Permanent stoma	Closed stoma	p-value (chi2)	CD	UC	p-value (chi2)	Stoma	No stoma	p-value (chi2)
Number of patients	111	65		93	83		176	176
Diagnosis at ostomy time    Crohn    UC/IBDU	62 (55.9%)49 (44.1%)	31 (47.7%)34(52.3%)	0.295				94 (53.4%)82 (46.6%)	95 (54%)81 (46%)	0.915
Gender    Male    Female	64 (57.7%)47 (42.3%)	34(52.3%)31(47.7%)	0.490	49 (52.7%)44 (47.3%)	49(59.04%)34 (41%)	0.397	98 (55.7%)78 (44.3%)	104(59.1%)72 (40.9%)	0.518
Family history of IBD (y/n)	18 (16.2%)	4 (6.1%)	0.051	11 (11.8%)	11(13.25%)	0.775	22 (12.5%)	22 (12.5%)	1.00
NSAID intake (y/n)	16 (14.4%)	8 (12.3%)	0.694	14(15.05%)	10(12.05%)	0.562	24 (13.6%)	30 (17%)	0.375
Other medical history (y/n)	31 (28%)	18 (27.7%)	0.973	28 (30.1%)	21 (25.3%)	0.478	49 (27.8%)	52 (29.5%)	0.724
Age at ostomy timeMedian, q25 –q75,min–max	43, 31–576–81	40, 29–5114–76	0.097	42, 30–526–81	41, 30–5314–79	0.0002	41.6, 30.6– 52.76–81	42.6, 31.7–55.49–88	0.6645
Disease duration at ostomy time    Median, q25 –q75,    min–max	11.6, 6–181–44	11, 6–171–33	0.563	14, 8–231–44	8, 4–141–43	0.1045	11.5, 6–181–44	12.4, 4–20–53	0.8385
Occurrence ofComplicationsExtra-intestinal manifestationHospitalization related to IBD	92 (82.9%)70 (63.1%)67 (60.4%)	56(86.1%)47(72.3%)42(64.6%)	0.5670.2100.575	76 (81.7%)62 (66.7%)59 (63.4%)	72 (86.7%)55 (62.3%)50 (60.2%)	0.3630.9550.663	148(84.1%)117(66.5%)109 (62%)	132 (75%)122(69.3%)58 (33%)	0.0340.5680.001
Therapy with…    5-ASA    Antibiotics    Immuno-modula- tors    Biologics    Steroids	88 (79.3%)87 (78.4%)101 (91%)81 (73%)104 (93.7%)	51(78.5%)46(70.8%)59(90.8%)54(83.1%)63(96.9%)	0.8980.2570.9610.1260.348	60 (64.5%)72 77.4%)89 (95.7%)77 (82.8%)89(95.7%)	79 (95.2%)61(73.5%)71(85.5%)58(69.9%)78 (94%)	0.0010.5450.020.0430.604	139 (79%)133(75.6%)160 (91%)135(76.7%)167(94.9%)	159(90.3%)114(64.8%)174(98.9%)142(80.7%)172(97.7%)	0.0030.0270.0010.3620.158

Comparison of the baseline variables in stoma and non stoma patients, patients with permanent or closed stoma as well as patients with CD and UC.

Course of disease

First we aimed to investigate disease activity after ostomy in the control group and both ostomy-groups (i.e. the permanent and closed), as well as according to subtype of IBD. The mean CDAI after stoma construction surgery was significantly lower compared to CD patients in the control group not receiving ostomy. Similarly, the maximal CDAI was significantly reduced after ostomy. In contrast, we did not observe such benefits in MTWAI in UC patients with stoma in comparison to the control group (Fig 1).

Fig 1

Comparison of mean and maximal Crohn’s Disease Activity Index (CDAI) and Modified Truelove and Witts Activity Index (MTWAI) in patients with and without stoma.

Furthermore, we identified a lower fraction of EIMs in IBD patients undergoing ostomy in comparison to patients without stoma despite matching the control groups according to several baseline characteristics including previous EIM. Regarding medical therapy, a lower fraction of treatment with 5-ASA, immuno-modulators, biologics as well as steroids was observed in IBD patients with stoma. Moreover, we did not find stoma application to be associated with more complications, however an increase in hospitalization rates was observed. (Table 1).

Next, we aimed to investigate the fraction of patients with permanent or closed stoma and whether stoma type associates with the course of disease and complications. We therefore compared 111 patients with permanent stoma to 65 patients whose stoma has been closed. Of the 111 patients with permanent stoma 62 (55.9%) were experiencing CD and 49 (44.1%) from UC. In the closed stoma group 31 (47.7%) CD and 34 (52.3%) UC patients, respectively, were included. As expected after colectomy in UC, we found a significantly lower median UC disease activity in patients with permanent stoma. Similar results were observed regarding maximal MTWAI after ostomy (Fig 2). Furthermore, we found, that UC patients with closed stoma were significantly more often treated with antibiotics than participants with permanent stoma (2% vs. 17.7%, p = 0.012, S1 Fig). In contrast in CD, no significant decrease in mean nor maximal disease activity was observed (Fig 2).

Fig 2

Mean and maximal disease activity in permanent vs. closed stoma in patients with Crohn’s Disease and patients with Ulcerative colitis.

Regarding medication use, hospitalization, EIM as well as complications permanent stoma application did not appear to be associated with inferior outcomes compared to closed ostomy but stoma patients in general where more often hospitalized than patients without (Table 1).

Psychological wellbeing

To assess the long-term impact on closed/permanent ostomy on psychological well-being, we aimed to compare the psychological wellbeing indices before and after ostomy and investigate whether there are differences in the evolution of these indices in patients with permanent vs. closed ostomy. When comparing patients with stoma to patients without stoma no differences could be found in the total scores of IBDQ, HADS and effort-reward ratio. However, patients with stoma scored higher in PDS total score. In the patient population with stoma, we did not observe significant differences in the total scores of IBDQ, HADS, PDS and effort-reward-imbalance ratio between patients with persistent vs. closed stoma either. Of note, we observed a lower PDS avoidance score in patients with permanent stoma after ostomy with an increase in contrast in the closed stoma group (before 5 vs. 3, p = 0.036, after 3.8 vs. 4.5, p = 0.672, S2 Fig). Looking at CD and UC patients separately, again no significant differences were observed in the total scores in line with the above-mentioned data (Fig 3A–3D). However a decrease in PDS avoidance score could be observed in CD patients with permanent stoma, after ostomy with the opposite in the closed ostomy group before (5 vs. 1, p = 0.018, after 3.8 vs. 4, p = 0.83, S3 Fig) Regarding the PDS Total score before vs. after ostomy in CD patients with closed ostomy, we found a more than three-fold increase whereas a decrease was observed in those with permanent ostomy (PDS Total Score in patients with closed vs. permanent ostomy, respectively, before 12.2 vs. 4, p = 0.049, and after 8.1 vs. 14, p = 0.99 ostomy, S4 Fig). Moreover, regarding the IBDQ social function score, a significant difference in CD patients with permanent or closed ostomy alone was observed before but not after ostomy (before 23.3 vs. 34, p = 0.001, after 25.5 vs. 33.7, p = 0.06, S5 Fig). Nevertheless, when comparing the overall IBD population with stoma to the patient group without stoma IBDQ social function scores were lower in the ostomy group (27.8 vs. 30.7, p = 0.035 and 30 vs. 34, p = 0.004, S6 Fig). Furthermore, we also observed higher posttraumatic stress (Fig 3C) with increased symptoms associated with ostomy (4 vs. 2.4, p = 0.005, S7 Fig) in patients undergoing ostomy in comparison to those without stoma. In line with that, a significantly higher re-experiencing score was found in comparison to patients without ostomy (2.3 vs. 1.3, p = 0.018, S8 Fig).

Fig 3

Comparison of different psychological scores to assess wellbeing of IBD patients.

A) Comparison of median and minimal and maximal scores of Inflammatory Bowel Disease Quality of Life Questionnaire Total Score (IBDQ Total Score) in different patient groups as an indicator of health related quality of life. B) Comparison of median and minimal and maximal scores of Hospital Anxiety and Depression Scale (HADS) Total Score in different patient groups as an indicator of anxiety. C) Comparison of median and minimal and maximal scores of Posttraumatic Diagnostic Scale (PDS) Total Score in different patient groups as an indicator of Post-Traumatic Stress Disorder. D) Comparison of median and minimal and maximal scores of Effort-Reward Ratio in different patient groups.

In summary it can be stated that IBDQ, HADS and effort reward ratio do not differ between either the stoma group an the control group, the persistent and closed ostomy group nor UC and CD patients. However, PTSD symptoms are higher in stoma patients in general and especially in the permanent stoma group. Similarly, IBDQ social function score decreases after ostomy. Moreover, especially CD patients show noticeable changed in scores after ostomy. This includes lower PDS avoidance score and PDS total score in patients with permanent stoma.

Working capacity and invalidity pension

Comparing working capacity overall, we found, that 63.8% of patients with stoma were working at any point during the SIBDCS compared to 71.3% of the IBD patients without stoma (Fig 4A). Any absenteeism from work at least once during the follow-up in the cohort study was more frequently reported in IBD patients with vs. without stoma (Fig 4B).

Fig 4

Working capacity and invalidity pension related data in different groups.

A) Working patients in different patient groups. B) Number of patients in different groups absent from work at least once during participation in the Swiss Inflammatory Bowel Disease Cohort Study. C) Patients in different groups with disability benefits.

A lower fraction of working patients prior to stoma construction surgery was identified in the permanent stoma group, compared to the closed stoma group (Fig 4A). Congruently, a higher fraction of patients receiving disability benefits was found in patients with permanent vs. closed stoma prior to the time of stoma construction surgery (Fig 4C). After ostomy an overall lower fraction of working patients could be observed in permanent as well as closed stoma patients with an even larger decrease of working patients in the closed stoma group (Fig 4A). Looking at CD and UC in separate, an analogous trend was observed.

Furthermore, the fraction of patients receiving a disability insurance was higher amongst patients with permanent stoma and increased after stoma surgery. In contrast, this fraction was even lower in patients with closed stoma compared to the matched IBD patients without stoma surgery (Fig 4C).

In addition, more patients in the permanent stoma groups reported any absence from work at the follow-up visits, specifically in CD (Fig 4B).

Discussion

In our study we aimed to investigate the impact on closed and permanent stoma surgery in patients with IBD on relevant patient-centered outcome parameters, including clinical disease characteristics, psychological parameters and working capacity. Our results indicate, that stoma formation in general–regardless of closed vs. permanent ostomy and against what several patients and physicians alike might expect–is not a priori associated with an adverse psychological outcome. Also, in appropriate CD patients diagnosed with severe disease, these patients may benefit from stoma application to reduce disease activity. However, this study design evidently was unable to provide a definite guidance on whether permanent or closed stoma represents the favored therapeutic strategy in these type of patients. On the one hand, we could did not distinguish between (or respectively perform separate analysis according to) the primary driving reason(s) for stoma closure. This primary motive often is not fully declared in medical records, and not seldomly, there may be a mixed bag of factors, driving the treatings physicians and affected patients towards the decision of preserving vs. reverting ostomy. In CD patients a high recurrence rate most commonly at the side of the anastomosis and/or ostomy is known [42]. It could therefore be speculated that specifically patients without inflammatory recurrence of CD could benefit more from closed ostomy, while these patients at the same time are more likely to have more favorable overall outcome parameters than their counterparts with recurrence.

Moreover, we have observed a significant decrease in medication and EIM in IBD patients in general after stoma application indicating a potential reduction in the severity of disease course. Our results are in line with those from Goudet et al. [43], who previously reported a reduction of EIM in UC after proctocolectomy, and also those from our own group [44]. It can therefore be concluded that patients with CD potentially could benefit from ostomy formation especially in those patients, with complicating course of disease, persistent activity of disease or EIM not being under adequate control and those patients with treatment-related adverse events.

This would be in line with the British Society of Gastroenterology consensus guidelines [6] as well as the Ulcerative Colitis Practice Guidelines in Adults [45] stating that surgery represents a valuable treatment option in case of failing medical therapy or intolerable medical side effects. Furthermore and as to be expected in a disease limited to the colon, we confirmed that also patients with UC can benefit from permanent stoma application as disease activity could be reduced significantly.

Of crucial note in this regard is the fact that permanent ostomy was non inferior to closed ostomy in IBD patients overall regarding medication use, hospitalization, EIM as well as complications.

As a limitation of our design enabling a matching process including amongst others disease severity and prior complications, we cannot exclude, that patients in both stoma groups a priori represent a fraction of a more difficult-to-treat patient population, acknowledging that any matching per se is likely to remain imperfect. Therefore, ever being in need of stoma formation surgery (be it closed or permanent) might constitute a surrogate parameter for a more severe course of disease, higher likelihood of complications and disability. Having this in mind and considering the relatively favorable results observed in our outcome parameters of interest in stoma vs. non-stoma IBD patients, one might assume, that the overall potential benefit of closed and permanent stoma formation may even have been underestimated.

As of today, to the best of our knowledge no study has been conducted comparing permanent with closed stoma in this particular patient group. It is generally well established that IBD may have an adverse impact on quality of life, however data after ostomy is controversial [16-19]. According to our data permanent stoma in both UC and CD compared to no stoma surgery at all as well as permanent vs. closed stoma surgery does not to translate into inferior or unfavorable outcomes with regard to clinical parameters, psychological well-being and disability. This indicates that IBD patients with an underlying robust indication for stoma surgery, either persistence of stoma or stoma closure surgery, do not appear to have a sustainably impact future psychological wellbeing. This contradicts previous studies indicating surgery to be a trigger for PTSD [22] and showing that patients with higher PTSD symptoms have more likely had surgery [46]. This correlates with the finding that patients in the SIBDCS with ostomy scored higher in the PDS total score, showed a higher avoidance of stimuli associated with ostomy and a higher re-experiencing score in the SIBDCS. This could however also be due to a relatively more severe course of disease (stoma as a surrogate for a more debilitating disease course, imperfect matching; as mentioned above) which has also been shown to impact severity of PTSD symptoms [46]. It has also to be stressed that none of the studies focused specifically on ostomy and that we were able to show a decrease in PDS avoidance score in patients with permanent ostomy and an increase in closed ostomy, suggesting a possible impact of stoma type (permanent/closed). It remains therefore possible, that in permanent stoma patients, PDS avoidance score could even be reduced after surgery. It can be speculated that there are fewer complications and thus hospitalizations also known to be a triggering factor in PTSD [22]. Furthermore a re-traumatization of patients by anew surgery could be prevented. This especially appeared to be the case in CD patients, indicating a lower susceptibility to PTSD symptoms of permanent stoma patients in general and CD patients in particular. In contrast a in 2019 published US study reported a greater susceptibility of CD patients for PTSD [47]. However no distinction between patients with ostomy and without ostomy and ostomy type (permanent, closed) was made.

Therefore, we may conclude that stoma type may not be the main factor influencing psychological well-being in IBD patients with stoma. However, our data revealed lower IBDQ social function score in stoma vs. non-stoma patients, which is in line with results from other studies indicating lower self-confidence as well as negative perceptions with regards to body image correlating with loneliness in patients after ostomy [48]. Nevertheless in our CD patients this lower score appeared to be improved after stoma application compared to patients not receiving ostomy, indicating a potential beneficial effect on quality of life in this patient group. Overall, our data indicates that specifically CD patients with a solid indication for stoma surgery, may experience a benefit from permanent ostomy.

Moreover, we observed that in stoma patients absenteeism from work was more frequent compared to patients without stoma. This evidently is to be expected, having in mind, that IBD patients in need for stoma formation represent a subgroup of patients with a distinctively severe course of disease. However and most importantly, our results indicate, that this difference in working capacity between patients with vs. without stoma formation was found to be rather minor (with only numerical but not significant overall difference, Fig 2A). Interestingly, a decrease in the fractions of patients actively working with a concomitant increase in patients receiving disability benefits were observed in closed and permanent ostomy patients after surgery. This suggests that the overall negative impact of any stoma formation on capacity to work is substantial. However, only numerically more patients with permanent ostomy were absent from work and the overall difference of working patients in closed vs. permanent stoma patients was rather small. This in conjunction with the overall substantial fraction of almost 20% [24] up to 30% [25] and more of IBD patients overall receiving an invalidity pension on the long-term indicates the following: Although IBD patients in need of a stoma surgery will be at increased risk for permanent work disability and this risk may be higher in patients were a permanent stoma is indicated. However, a substantial fraction of patients even those patients with permanent stoma formation are capable of continuing their work and the associated negative impact on working capacity in both closed and permanent stoma formation compared to IBD patients without stoma surgery is only moderate. Evidently, further studies are needed to investigate the detailed impact of closed and permanent stoma formation on work disability. This especially holds true in view of the overall limited numbers of patients with stoma surgery in the SIBDCS as well as the potentially remaining selection bias in this study, taking into account, that need for stoma surgery per se may represent one of the strongest indicator (or even surrogate parameter) of a debilitating course of disease. Both these aspects represent limitations of our work. Our work has also several strengths including the nationwide, multicenter prospective inclusion of unselected IBD patients with a long-term follow-up using a multitude of standardized outcome parameters, including a plethora of validated scores regarding psychological wellbeing.

In conclusion, according to our long-term prospective cohort database analysis we observed that IBD patient in need for closed and permanent stoma formation may benefit from this surgical intervention in terms of their luminal and extra-intestinal disease activity. Overall there appears to be only a moderate adverse impact of stoma formation surgery on work disability, even in patients with permanent stoma. Also and in contrary to what one might assume, we did not observe a consistent adverse impact of stoma formation on psychological well-being, neither in closed nor in permanent stoma surgery. Taken together, stoma surgery remains an important tool in the armamentarium of difficult-to-treat IBD patients and our results suggest, that potential downsides in terms of symptoms, quality of life and disability not seldomly feared by patients and potentially their treating physicians alike may be considerably over estimated.

Antibiotics used in UC patients before and after ostomy according to stoma type.

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Comparison of mean PDS Avoidance Score in patients with permanent vs. closed ostomy.

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PDS Avoidance Score before and after ostomy in CD Patients specifically.

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PDS Total Score in CD patients with permanent and closed ostomy before and after ostomy.

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IBDQ Social Function Score in CD patients comparing patients with and without ostomy.

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IBDQ Social Function Score in patients overall with and without ostomy.

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PDS Avoidance Score in patients with vs. without ostomy.

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PDS Re-experiencing score in IBD patients with and without ostomy.

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18 Jul 2022

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Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for inviting me to review this manuscript, but I found this an almost impossible task because of the poor grammar and sentence structure. For example, in the introduction, the sentence starting "The latter representing the standard procedure..." is awkward and difficult to understand.

In the methods section, there is a list of complications but it is unclear what the complications are thought to be of (stoma creation? disease process?) and unclear why the sentence is sitting in the middle of the paragraph.

On line 105, there is a reference to a questionnaire but it isn't clear what questionnaire - although I assume this relates to the IBDQ, the HADS and the PDS which are mentioned later. I am also unclear from the methods when the CDAI and Truelove/Witts were measured.

EIM is mentioned first in the results and not explained.

It appears under the "Course of Disease" heading that CDAI was measured in both Crohns and UC patients.

Finally, I am unclear as to how many of the patients with closed stomas had UC or Crohn's disease and how recurrent disease was measured / taken into account. A panproctocolectomy in someone with UC is, of course, curative, in a way that stoma closure in Crohn's disease may be related to recurrence (in that the anastomosis is usually the site of recurrent disease).

I have not been able to review the results because I do not fully understand the methods as they are currently written.

Having said all that, I'd be very interested/happy to read another draft of the paper.

Reviewer #2: The present study evaluates the long term psychosocial impacts of ostomy in a large Swiss cohort of IBD patients. This is an important area of research with limited existing data, especially over time, and evaluates different types of ostomy IBD patients live with. The study is well designed. Some of the data presentation can be improved upon, especially as it relates to the PDS/psychological well being scores (see below). The discussion needs to be re-written as it appears biased and does not include discussions about the poor outcomes found in this cohort. There is no incorporation of existing data on IBD-related PTSD, which is needed. With these edits the discussion will be more balanced and reflect the prevailing literature as well as the study's actual findings.

I have the following comments/edits that should be considered before publication:

Introduction:

Current estimates of IBD in the US are 3 million versus 1 million. Please amend and update citation.

Please clarify "biological vs. non-biological agents" as medications used to treat IBD.

Sentence starting on line 62 is a bit confusing. Please re-write stating the procedure versus "the latter" for clarity.

Line 78: There are new studies on post-traumatic stress in IBD by Pothemont et al. and Taft et al, please review and cite, especially since discussions of surgery are reported to be potential sources of medical trauma.

Methods:

Line 91: Please update language "suffering from" to "diagnosed with"

Results:

Line 162, line 190: Please update language "suffering from" to "experiencing"

In the table, there is no data for the smoking status line. Is this correct? If so, not sure it's useful to include.

It would be helpful if the data in the "Psychological Well Being" section into a table. As written, it's a bit difficult to follow the numbers pre-post across the different groups.

Line 226: How is the P value for the differences reported 0.99 with a 3-fold increase in PDS score? Please clarify.

Discussion:

The statement that ostomy is not associated with adverse psychological impact conflicts with the findings that those undergoing ostomy report more post-traumatic stress symptoms and poorer social function. PTSD is a significant psychological comorbidity that is chronic without treatment, and likely has larger impacts on patient outcomes than anxiety and depression.

Line 275: Please update language "suffering from" to "diagnosed with"

Section starting on line 304 needs to be re-written. There is robust data regarding PTSD in IBD patients, including how surgery and hospitalizations may be traumatic. These studies need to be incorporated into the present PDS data and discussed.

Reviewer #3: Thank you for the opportunity to review this paper. The authors used a prospectively collected cohort of IBD patients to answer the question of how ostomies affect disease course, psychological well-being, quality of life, and working capacity. They used a propensity score analysis to match patients with and without ostomy. They found lower disease activity in patients after stoma surgery, similar disease-specific QOL, psychological discress, and stress at work in patients with vs without stoma and patients with a permanent stoma vs patients whose stomas were closed. There was a modest adverse effect on working capacity for patients who had a stoma; and a significant reduction in working capacity in Crohn’s patients with a permanent stoma vs stomas that had been closed. My questions are:

1. Did the control group have surgery that did not involve a stoma? Or no surgery at all? Or did some have surgery, some did not, but none of them had a permanent or temporary ostomy?)

2. How did you manage patients with temporary stomas that have not yet been closed in the analyses? Were they considered part of the “permanent stoma” group, or were they not included in the study?

3. On p7, it is stated that patients were eligible if they completed a minimum of one questionnaire before stoma creation, one while they had the stoma, and one after stoma closure. For those who did not have surgery resulting in stoma, what questionnaire completion metrics did they need to meet to be included? Also, are they filling out all of these instruments (IBDQ, HADS, PDS) in one questionnaire, or at least one of the 3 questionnaires?

4. How often was disease severity quantified in this cohort, and did the frequency of disease severity scoring impact eligibility?

5. When you compared control to overall stoma patients, did you compare their scores at that time that they had their stomas (for those who had temporary stomas)? Or after their stomas were closed?

6. For UC patients with stoma compared to those without, there was no difference in disease severity. Presumably these are patients who have had total proctocolectomy with end ileostomy or who had IPAA with temporary stoma compared with patients who have had one-stage IPAA or patients who have not had any surgery at all – please confirm as this is not clear. Were patients with total colectomy with end ileostomy included in this analysis? That is, patients who still had a rectum in place – and thus are halfway through their surgical treatment?

7. For the outcome of medical therapy, are patients with UC who have undergone colectomy or proctocolectomy with stoma being compared to patients who haven’t had surgery and those who had one-stage IPAA? Patients who have had surgery, with or without stoma, for UC would be expected to be off medications completely. When you analyze just Crohn’s disease patients, do you see the same effect?

8. Can the authors comment on why there might be a higher PDS score in patients whose stomas have been closed compared to those with permanent stomas?

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Reviewer #3: No

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20 Aug 2022

Manuscript Submission “Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD Cohort Study patients.”

Dear Editorial Board,

We thank the reviewers and the editorial board very much for their careful consideration of our manuscript. We certainly feel that the suggestions from the reviewer's and the editorial board could significantly improve the manuscript. In addition, we feel, that we could address most of the valuable comments. Please find attached a point-by-point response with referral to the respective changes in the manuscript which we attached in track change form. Again, we would like to take this opportunity to thank the journal and the reviewers for considering our work.

We are happy to respond to any potential further questions.

In the name of all authors, Rahel Bianchi and Luc Biedermann

Reviewer: 1

Comments to the Author

Thank you for inviting me to review this manuscript, but I found this an almost impossible task because of the poor grammar and sentence structure. For example, in the introduction, the sentence starting "The latter representing the standard procedure..." is awkward and difficult to understand.

We thank the reviewer for this comment. According to his suggestion on English language we performed a careful review of the entire manuscript and performed several adaptations in terms of language and wording which are apparent in track change mode of the manuscript. As the sentence. "The latter representing the standard procedure..." was not only difficult to read for this reviewer but for reviewer two as well we agree that it is very difficult to read and have therefore applied changes specifying the procedure. Otherwise, and despite the concerns of Reviewer#1 which we of course kindly acknowledge, we would kindly like to add, that amongst the writers, there are numerous experienced clinical and basic scientists with respective experience in English and scientific writing. Moreover, this “almost impossible” task neither appeared to be equally difficult for Reviewer#2 and #3 nor the co-authors.

In the methods section, there is a list of complications but it is unclear what the complications are thought to be of (stoma creation? disease process?) and unclear why the sentence is sitting in the middle of the paragraph.

We thank the reviewer for this important and well-taken comment. We fully agree, that we missed the occasion to make it entirely clear to the reader, what the exact nature of these described complications was. In this case, we were referring to a composite of a group of major complications associated with CD and UC per se. We have changed the manuscript accordingly (line 183 and following paragraph) and changed the text to reduce confusion about the definition of complications in the middle of the paragraph.

On line 105, there is a reference to a questionnaire but it isn't clear what questionnaire - although I assume this relates to the IBDQ, the HADS and the PDS which are mentioned later.

To gather data for the Swiss IBD Cohort Study patients and physicians are asked to fill out a number of questionnaires including medical (diagnosis, smoking status, pregnancy, current severity of disease, clinical course, past and current therapy, adverse events of therapy, supplementation therapy, laboratory analysis, flare ups and triggering factor, new exams and outcomes, disease complications, disease location, surgery, extraintestinal manifestations, fissures, abscesses, fistula and stenosis,), psychological (IBDQ, HADS, PDS, Efford-Reward-Ratio) and work related data (working status, absence of work, disability pension) once a year. Indeed, these questionnaires include the validated scores, mentioned by Reviewer#1. Having said that, we agree with the reviewer that he term “Questionnaire” is not clear. Therefore, we have specified it in line 191.

I am also unclear from the methods when the CDAI and Truelove/Witts were measured.

We agree with the reviewer that this is not only a crucial point but not sufficiently addressed in the methods section. CDAI and MTWAI were measured when the patients were included in the study as well as in the annual follow ups. We have added this information to the manuscript at line 209 and 210 and thank the reviewer for pointing out this issue.

EIM is mentioned first in the results and not explained.

We thank the reviewer again for this important comment. We completely agree that EIM have to be mentioned in the methods and explained. We changed the manuscript accordingly and appropriately introduced the term (line 180).

It appears under the "Course of Disease" heading that CDAI was measured in both Crohns and UC patients.

This is indeed an important remark as the text in the manuscript does not sufficiently distinguish between the two groups and therefore one could come to the assumption that CDAI was used for CD and UC patients. We have changed the manuscript accordingly at line 275 and 279.

Finally, I am unclear as to how many of the patients with closed stomas had UC or Crohn's disease and how recurrent disease was measured / taken into account. A panproctocolectomy in someone with UC is, of course, curative, in a way that stoma closure in Crohn's disease may be related to recurrence (in that the anastomosis is usually the site of recurrent disease).

We thank the reviewer for this important comment and provided information about all the groups including the patients with closed stoma in figure one. In patients with closed stoma 47.7% had CD and 52.3% were diagnosed with UC which is likewise mentioned in the manuscript at line 309. Therefore, this important piece of information as mentioned by Reviewer#1 is readily available. Recurrent disease was not taken into account in the CD group when performing the analysis as we wanted to provide a sufficient cohort size and there was no scheduled, mandatory or standardized procedure to investigate for recurrence of disease. This represents one limitation of a cohort study design, as compared to a prospective protocol-guided investigation. However, we feel that the reviewer mentions a crucial fact in this comment regarding a high recurrence rate of Crohn’s disease especially in ileostomy which should be discussed as it provides one potential explanation, as to why no difference could be observed when comparing disease activity in UC patients with permanent or closed stoma (a respective paragraph has been included in the discussion starting at line 433).

Reviewer: 2

Comments to the Author

Current estimates of IBD in the US are 3 million versus 1 million. Please amend and update citation.

We thank the reviewer for this important comment. We have updated the introduction accordingly using a more current and less conservative estimate of the US patient numbers including a respective reference (line 124).

Please clarify "biological vs. non-biological agents" as medications used to treat IBD.

We would like to thank the reviewer for pointing out this relevant difficulty to understand both terms and their exact meaning. We have therefore specified the terms with examples on line 129 and 130.

Sentence starting on line 62 is a bit confusing. Please re-write stating the procedure versus "the latter" for clarity.

We agree with Reviewer #1 and #2 who both suggested to change this sentence as it is difficult to read. As we would like to provide an easy readable text to readership we made the appropriate changes to the manuscript text (now line 134).

Line 78: There are new studies on post-traumatic stress in IBD by Pothemont et al. and Taft et al, please review and cite, especially since discussions of surgery are reported to be potential sources of medical trauma.

We again thank the reviewer for this comment regarding post traumatic stress in IBD patients and encouraging us to include important work on post-traumatic stress to be incorporated in this paper. Indeed, these studies undermine the importance of surgery and medical procedures in general for the development of post-traumatic stress symptoms. Therefore, we have included these studies in the introduction (Pothemont et al., Patient Perspectives on Medical Trauma Related to Inflammatory Bowel Disease, J Clin Psychol Med Settings, 2021) (lines 153-157) as well as the discussion (Pothemont et al., Patient Perspectives on Medical Trauma Related to Inflammatory Bowel Disease, J Clin Psychol Med Settings, 2021, Taft et al. Posttraumatic Stress in Patients with Inflammatory Bowel Disease: Prevalence and relationships to Patient-Reported Outcomes, Inflamm Bowel Dis, 2022 and Taft et al. Initial Assessment of Post-traumatic Stress in an US Cohot of Inflammatory Bowel Disease Patients, Inflamm Bowel Dis, 2019) starting at line 478.

Line 91: Please update language "suffering from" to "diagnosed with"

Line 162, line 190: Please update language "suffering from" to "experiencing"

Line 275: Please update language "suffering from" to "diagnosed with"

These suggested changes have been incorporated in the manuscript.

In the table, there is no data for the smoking status line. Is this correct? If so, not sure it's useful to include.

The reviewer is correct that there is no data in the evaluated group in our table. This is due to the fact, that the smoking status during surgery procedures, was not optimally assessed. We therefore decided to entirely delete this from our table and thus updated table one accordingly.

It would be helpful if the data in the "Psychological Well Being" section into a table. As written, it's a bit difficult to follow the numbers pre-post across the different groups.

We would like to thank the reviewer for this comment. We are fully aware that it can be difficult especially as mentioned when switching between the different groups. We therefore provided several figures especially for psychological wellbeing and work ability as we felt this was an easy to comprehend way to show our data. We also added a paragraph summarizing the results starting at line 371. However, if a table is preferred we are more than happy to provide all the data accordingly.

Line 226: How is the P value for the differences reported 0.99 with a 3-fold increase in PDS score? Please clarify.

We thank the reviewer for this comment as we agree that it is difficult to understand what is shown in the text. The roughly 3-fold increase refers to the PDF PRIOR ostomy and here, for this value we found a significant difference. However, after ostomy, the PDS between the two groups is roughly similar. Although the median value appears robustly different. The confidence interval is the IQR is similar and thus also no significant differences (p-value 0.99) was found.

The statement that ostomy is not associated with adverse psychological impact conflicts with the findings that those undergoing ostomy report more post-traumatic stress symptoms and poorer social function. PTSD is a significant psychological comorbidity that is chronic without treatment, and likely has larger impacts on patient outcomes than anxiety and depression.

Section starting on line 304 needs to be re-written. There is robust data regarding PTSD in IBD patients, including how surgery and hospitalizations may be traumatic. These studies need to be incorporated into the present PDS data and discussed.

We thank the reviewer for this important annotation. We fully agree with the reviewer that it is crucial to incorporate the newest data provided especially by Taft et al. in the discussion as it shows clearly in multiple publications the negative impact of surgery, hospitalization and severity of the disease on PTSD symptoms. We have therefore included several studies starting at line 478 (Pothemont et al., Patient Perspectives on Medical Trauma Related to Inflammatory Bowel Disease, J Clin Psychol Med Settings, 2021, Taft et al. Posttraumatic Stress in Patients with Inflammatory Bowel Disease: Prevalence and relationships to Patient-Reported Outcomes, Inflamm Bowel Dis, 2022 and Taft et al. Initial Assessment of Post-traumatic Stress in an US Cohot of Inflammatory Bowel Disease Patients, Inflamm Bowel Dis, 2019) and discussed them in them in the manuscript. We also would like to add that we were aware that surgery can be a traumatic event, however our data does not suggest stoma type (permanent/closed) to be a factor in PTSD formation.

Reviewer: 3

Comments to the Author

Did the control group have surgery that did not involve a stoma? Or no surgery at all? Or did some have surgery, some did not, but none of them had a permanent or temporary ostomy?)

We thank Reviewer#3 for this important question. With regards to UC patients it is easy to answer, as in Switzerland no colonic resection in UC patient (virtually all will be total proctocolectomy; only rarely colectomy with rectal sparing) is performed without a temporary (sometimes even a permanent) stoma application; either as a (modified) two-step or more frequently three step procedure. With regards to CD patients undergoing segmental intestinal resection the situation is a bit more complex indeed. Virtually all patients with emergent resection in view of a penetrating complication (fistula formation and/or abscess) will receive a temporary stoma. In contrast, segmental resection – most often performed for fibrostenosis or refractory inflammatory and mixed fibro-inflammatory stenosis – in a more elective fashion is performed in the majority of cases without stoma. We feel, that these patients would not represent an ideal control group, as patients with for instance an ileal fibrostenosis undergoing ileocecal resection typically represent another and rather distinctively different group of patients.

How did you manage patients with temporary stomas that have not yet been closed in the analyses? Were they considered part of the “permanent stoma” group, or were they not included in the study?

Again, this is an important point. Indeed, it lies in the nature of the definition of temporary vs. permanent stoma formation, that any temporary ostomy might one day be reverted. For instance, this is often a remaining hope for patients with refractory high burden peri-anal CD having undergone diversion ostomy. Could one call this a permanent stoma e.g. 2 years after the initial surgical step or is there a hope, that with emerging medical therapy options, one day, the stoma might be reverted and thus in hindsight would be characterized as a temporary stoma?

Evidently, the latter is possible. In our study, every patient with sustained ostomy present at follow-up after initial stoma formation surgery was considered as “permanent” stoma in our analysis.

On p7, it is stated that patients were eligible if they completed a minimum of one questionnaire before stoma creation, one while they had the stoma, and one after stoma closure. For those who did not have surgery resulting in stoma, what questionnaire completion metrics did they need to meet to be included? Also, are they filling out all of these instruments (IBDQ, HADS, PDS) in one questionnaire, or at least one of the 3 questionnaires?

How often was disease severity quantified in this cohort, and did the frequency of disease severity scoring impact eligibility?

For those who did not have surgery resulting in stoma, what questionnaire completion metrics did they need to meet to be included?

We thank the reviewer for these important questions and are happy to clarify them further. The IBDQ, HADS and PDS are all included in one questionnaire and have to be fully completed by the patient without their treating physician (PRO). Disease severity was assessed at the minimum for a least three times for all patients. Disease severity is also measured by a questionnaire every time psychological scores are evaluated as well. The follow up questionnaires were sent to patients and their physicians once a year and had to be completed at least at year 1, 3 and 5 for eligibility in this study. The frequency of disease severity scoring therefore did not impact eligibility. We agree that the inclusion criteria especially for the control group is not explained thoroughly enough. We added the information therefore at lines 205-207.

When you compared control to overall stoma patients, did you compare their scores at that time that they had their stomas (for those who had temporary stomas)? Or after their stomas were closed?

We thank the reviewer again for this comment as we are happy to clarify, that we compared the scores at the time the stoma was in place. We agree that this is not fully clear, we adapted the manuscript accordingly. (Line 206)

For UC patients with stoma compared to those without, there was no difference in disease severity. Presumably these are patients who have had total proctocolectomy with end ileostomy or who had IPAA with temporary stoma compared with patients who have had one-stage IPAA or patients who have not had any surgery at all – please confirm as this is not clear. Were patients with total colectomy with end ileostomy included in this analysis? That is, patients who still had a rectum in place – and thus are halfway through their surgical treatment?

We thank the Reviewer#3 again for this important remark. As mentioned above in our answer to a previous comment: there is no one-stage IPAA performed in Switzerland. Indeed, patients undergoing a presumptive 3 step proctocolectomy or colectomy with rectum left in place (as mentioned above, this only rarely performed in Switzerland, if at all, virtually always in young females with child-bearing potential) and without further continuing the procedure of pre-designated stoma formation but preference of sustained ileostomy (with or without rectum in place) were included here. In our experience, there is a small fraction of patient deciding to refrain from continuation of surgical step half-way through.

For the outcome of medical therapy, are patients with UC who have undergone colectomy or proctocolectomy with stoma being compared to patients who haven’t had surgery and those who had one-stage IPAA?

As mentioned above, there is no comparison to one-stat IPAA. We however do agree with Reviewer#3 that this is a relevant question. Our cohort study however, is not ideal to study such potential differences in outcome and patient preferences between one, two and three step IPAA procedure. In the last years, there first has been a trend suggesting a potential advantage of three-step procedure, while more recently two step procedures - above all the modified version – may have a comparable outcome and low fraction of complications at least in tertiary referral centers. The latter might be one of the main concerns for extrapolation of favourable modified two-step data. Again, the SIBDCS certainly is not the ideal format to investigate this highly important and relevant issue.

Patients who have had surgery, with or without stoma, for UC would be expected to be off medications completely. When you analyze just Crohn’s disease patients, do you see the same effect?

We thank the reviewer for this comment. The comparison between CD patients with permanent and closed stoma we can observe a decrease of medication use in both group without a significant difference between them.

Can the authors comment on why there might be a higher PDS score in patients whose stomas have been closed compared to those with permanent stomas?

We would like to thank the reviewer for this comment but unfortunately it was not entirely clear to us to which specific PDS score Reviewer#3 was primarily aiming to in the question. As we suppose it was PDS avoidance score we attribute the higher score in patients with closed stoma to possible post-operative complication and re-experiencing the trauma from the first surgery when the stoma was formed again. We agree with the reviewer that this has not been addressed sufficiently. The manuscript has been changed accordingly (starting at line 495).

Yours sincerely,

Rahel Bianchi and Luc Biedermann in the name of all coauthors

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

2 Sep 2022

Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD Cohort Study patients.

PONE-D-22-09385R1

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Reviewers' comments:

7 Sep 2022

PONE-D-22-09385R1

Effect of closed and permanent stoma on disease course, psychological well-being and working capacity in Swiss IBD Cohort Study patients.

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