ABSTRACT
Aims
The Japan COVID‐19 Survey and the Questionnaire for Inflammatory Bowel Disease (J‐DESIRE) identified multiple factors associated with anxiety regarding the novel coronavirus disease 2019 (COVID‐19). However, no regional differences in anxiety were observed. In this post hoc analysis of J‐DESIRE, we investigated the relationship between the municipal population size at the place of residence (MPSPR) and anxiety among patients with IBD in Japan during the COVID‐19 pandemic.
Methods and Results
We analyzed 2958 questionnaires collected from patients with IBD aged ≥ 16 years between March 2020 and June 2021. The primary endpoint was the association between the visual analogue scale (VAS) scores of anxiety and MPSPR during the COVID‐19 pandemic. The mean VAS score for anxiety was higher than the overall mean VAS score in municipalities with large and small populations, while it was lower in municipalities with medium populations. Therefore, we categorized the population into three groups based on MPSPR: ≤ 150 000, 150 001–1 000 000, and ≥ 1 000 001. The three groups had different background factors, contents of anxiety, and sources of information regarding therapeutic drugs. These differences may have led to differences in the degree and content of anxiety.
Conclusions
We investigated the association between anxiety in Japanese patients with IBD and MPSPR nationwide during the COVID‐19 pandemic in Japan. The results obtained in this analysis are useful not only in special situations such as the COVID‐19 pandemic but also for considering regional differences in medical care.
Keywords: anxiety, COVID‐19, inflammatory bowel disease, population, questionnaire survey
1. Introduction
The coronavirus disease (COVID‐19) was first detected in Wuhan, China in 2019 and quickly spread worldwide [1]. COVID‐19 was declared a global pandemic by the World Health Organization in March 2020, and many countries implemented lockdowns to prevent its spread. As a result, the lifestyles of many people around the world changed significantly, and their daily lives had been greatly affected. In addition to anxiety regarding COVID‐19 infection, restrictions on daily life had a negative psychological impact on many people [2, 3].
Inflammatory bowel disease (IBD) consists of two major disease types: ulcerative colitis (UC) and Crohn's disease (CD). IBD occurs at a young age, often relapses, and requires lifelong treatment [4]. Therefore, during the COVID‐19 pandemic, patients with IBD faced a significant dilemma between the risk and anxiety of SARS‐CoV‐2 infection associated with visiting a medical institution and the risk and anxiety of disease worsening due to postponing the visit [5, 6, 7, 8, 9, 10, 11, 12].
There are large differences in the causes of anxiety due to the COVID‐19 pandemic depending on regional and national characteristics and medical conditions. However, no large‐scale studies on anxiety due to the COVID‐19 pandemic have previously been conducted in Japan. Therefore, we conducted a questionnaire survey to investigate the anxiety and behavioral changes of Japanese patients with IBD during the COVID‐19 pandemic. The study was called “The Japan COVID‐19 Survey and the Questionnaire for Inflammatory Bowel Disease (J‐DESIRE)” [13]. The J‐DESIRE study identified several factors related to anxiety. To compare regional differences in anxiety, medical institutions were divided into seven regions (Hokkaido District, Tohoku, and Hokuriku District, Kanto District, Tokai‐Chubu District, Kansai District, Chugoku, and Shikoku District, and Kyushu and Okinawa District). However, no regional differences in anxiety were found.
The results of the J‐DESIRE study also showed that many patients spent more than an hour commuting to the hospital. Therefore, to examine regional differences, it was necessary to consider the location of the patient's residence rather than the location of the medical institution.
In this post hoc analysis of the J‐DESIRE study, we focused on the location of the patient's residence rather than that of the hospital and also on the population size at the municipal level, which is a smaller unit than seven regions or prefectures. We then investigated the relationship between the municipal population size at the place of residence (MPSPR) and anxiety in Japanese patients with IBD during the COVID‐19 pandemic.
2. Methods
2.1. Patient Recruitment and Questionnaire
This study protocol was approved by the institutional review board of Sapporo Medical University and registered publicly on the UMIN registration (No. UMIN000041191).
Details regarding patient recruitment and questionnaire content are provided in the J‐DESIRE study [13]. Briefly, the recruitment period was from March 2020 to June 2021, and 30 hospitals and 1 clinic recruited patients with IBD aged ≥ 16 years. At each recruiting institution, patients with IBD were asked to complete a paper‐based questionnaire regarding COVID‐19 after obtaining written consent. Within 2 weeks of distribution, the completed questionnaires were returned to the Department of Gastroenterology at the Sapporo Medical University Hospital.
The questionnaire focused on the impact of COVID‐19 on anxiety related to IBD, disease activity, medical examination, IBD medication, and prevention of infection. The part of the questionnaire that requires quantitative evaluation was rated on a 10‐point visual analogue scale (VAS). The questionnaire is published in the Supporting Information of the J‐DESIRE study [13].
2.2. MPSPR
In Japan, the Statistics Bureau, Ministry of Internal Affairs and Communications conduct a census every 5 years to clarify the population status.
The MPSPR of the cities, towns, and villages where patients with IBD responded to the questionnaire was retrieved from the complete 2020 Census [14]. We also collected the population density data. Additionally, Tokyo's 23 wards were classified as one special ward instead of separate wards.
2.3. Statistical Analysis
Descriptive statistics were reported as means and standard deviations (SD) for continuous variables (10‐point VAS scores) and proportions for categorical variables. Two or more continuous variable groups were compared using the Student's t test. Dichotomous variables in the three groups were compared using the Pearson's test. Statistical significance was set at p < 0.05. All analyses were performed using JMP Pro version 15 (SAS Institute, Cary, NC). No imputation of missing data was performed.
3. Results
3.1. Overall Demographics and Clinical Characteristics
In the previous J‐DESIRE study, a total of 3790 questionnaires were distributed, of which 3049 (80.4%) were returned, 17 were excluded due to withdrawal of consent, and 3032 questionnaires were analyzed. In this post hoc analysis of the J‐DESIRE study, an additional 74 questionnaires were excluded due to the absence or insufficient description of the municipality of the place of residence, resulting in a final analysis of 2958 questionnaires (Figure 1). Tables S1 and S2 show the demographic data and treatment details for all participants (Tables S1 and S2).
FIGURE 1.
Flowchart of participants. In the previous J‐DESIRE study, a total of 3790 questionnaires were distributed, of which 3049 (80.4%) were returned; 17 were excluded due to withdrawal of consent, and 3032 questionnaires were analyzed. In this J‐DESIRE post hoc study, an additional 74 questionnaires were excluded due to the absence or insufficient description of the municipality of residence, resulting in a final analysis of 2958 questionnaires. J‐DESIRE: The Japan COVID‐19 Survey and the Questionnaire for Inflammatory Bowel Disease.
3.2. Relationship Between MPSPR and Anxiety
The primary endpoint of this study was the association between the VAS scores of anxiety and MPSPR during the COVID‐19 pandemic. Patients resided in 524 municipalities. The population size and number of cases in each municipality are shown in Table S3. Cases were concentrated in some municipalities. Figure 2a shows the relationship between the MPSPR and mean VAS score of anxiety. There was no simple correlation between population size and anxiety. However, compared to the overall mean score of anxiety, the VAS score of anxiety was high in municipalities with large or small populations and low in those with intermediate populations. As shown in Figure 2b, the mean VAS score for anxiety was higher than the overall mean VAS score in municipalities with large and small populations, while it was lower in municipalities with medium populations. Therefore, we divided the population into three groups based on MPSPR. The three groups were divided by residential population of 150 000 and 1 000 000. We then defined groups whose MPSPR was ≤ 150 000, 150 001–1 000 000, and ≥ 1 000 001 as Group A, Group B, and Group C, respectively. Figure 2c shows the proportion of Group A, Group B, and Group C for each anxiety VAS score, and Figure 2d shows the comparison of the mean VAS score of anxiety in each group. The VAS score of anxiety in Group A and Group C were significantly higher than that in Group B. We similarly examined the population density of the municipality of residence and the level of anxiety, but found no clear relationship (Figure S1).
FIGURE 2.
Relationship between municipal population size at the place of residence and anxiety. (a) shows the relationship between MPSPR and mean VAS score of anxiety. There was no simple correlation between population size and anxiety. However, compared to the overall mean anxiety score, VAS score of anxiety was high in municipalities with large or small populations. As shown in (b), (1) The mean VAS score for anxiety was higher than the overall mean VAS score in municipalities with large and small populations, while it was lower in municipalities with medium populations. (2) We divided the population into three groups by MPSPR. (3) The three groups were separated by a residential population of 150 000 and 1 000 000. (4) We defined groups as those with MPSPR ≤ 150 000 (Group A), 150 001–1 000 000 (Group B), and ≥ 1 000 001 (Group C). The population on the horizontal axis is expressed logarithmically. The red line shows the average VAS score of anxiety in each population. The green line shows the overall average VAS score of anxiety. The green scale bar shows the frequency distribution. Population size was collected from the complete 2020 Census (https://www.stat.go.jp/data/kokusei/2020/kekka.html. Accessed June 30, 2023). (c) shows the proportion of Group A, Group B, and Group C for each anxiety VAS score. (d) shows the comparison of the mean VAS score of anxiety in Group A, Group B, and Group C. The VAS scores of anxiety in Group A and Group C were significantly higher than those in Group B. MPSPR, Municipal population size at the place of residence; VAS, Visual analog scale.
3.3. Demographics and Clinical Characteristics of the Three Groups Divided by MPSPR
Figure S2 shows the timing of questionnaire collection for the three groups divided by MPSPR. The survey period spanned from March 2020 (mid‐second wave of the COVID‐19 pandemic in Japan) to June 2021 (end of the fourth wave of the COVID‐19 pandemic in Japan). During the survey period, Japan experienced two declarations of a state of emergency, which included travel restrictions to COVID‐19 epidemic areas, limitations on non‐essential outings, shortened restaurant operating hours, and event restrictions. The Ministry of Health, Labour and Welfare published the Japan IBD Task Force's guidelines on patient care and medications for Japanese physicians on the websites of the Japan IBD Research Group and the Japanese Society for Inflammatory Bowel Disease. However, the dissemination of this information may have varied depending on patients' geographic location and access to medical expertise. There was variation in the timing of questionnaire collection among the three groups divided by MPSPR. Table 1 shows the patient characteristics of the three groups divided by MPSPR. Compared to the other two groups, Group C was younger (Figure S3), had fewer married individuals, and more individuals who lived alone. No significant differences were observed in occupation. Compared to Group B, Group A and Group C had a high rate of CD and more cases of stoma. Although no significant differences were observed in medical history or self‐assessment of disease activity using the VAS, individuals in Group C were more likely to have had three or more surgeries than those in the other two groups. In Group B, the proportion of steroid suppositories used was higher and the proportion of Infliximab used was lower compared to the other two groups. The proportion requiring nutritional therapy was higher in Group A than in the other two groups (Table 2).
TABLE 1.
Participants' demographic characteristics at baseline in the three groups divided by population MPSPR.
| Characteristic n = 2958 | Group A n = 1003 a n (%) | Group B n = 1362 a n (%) | Group C n = 593 a n (%) | Pearson (p‐value) |
|---|---|---|---|---|
| Age (years); average ± SD | 44.5 ± 14.5 | 45.6 ± 15.0 | 43.8 ± 14.3 |
Group A vs. Group B: p > 0.05 Group A vs. Group C: p > 0.05 Group B vs. Group C: p = 0.0110 |
| Female sex; n (%) | 415/1003 (41.4) | 597/1362 (43.8) | 265/593 (44.7) | p > 0.05 |
| Married; n (%) | 583/995 (58.6) | 831/1356 (61.3) | 321/587 (54.7) | p = 0.023 |
| Co‐resident; n (%) | 861/995 (86.5) | 1147/1356 (84.6) | 453/590 (76.8) | p < 0.0001 |
| Occupation; n (%) | ||||
| Student | 41/999 (4.1) | 76/1350 (5.6) | 36/588 (6.1) | p = 0.0633 |
| Part‐time job | 142/999 (14.2) | 198/1350 (14.7) | 79/588 (13.4) | |
| Company employee | 430/999 (43.0) | 606/1350 (44.9) | 281/588 (47.8) | |
| Civil servant | 78/999 (7.8) | 94/1350 (7.0) | 34/588 (5.8) | |
| Self‐employed | 89/999 (8.9) | 84/1350 (6.2) | 34/588 (5.8) | |
| Homemaker | 84/999 (8.4) | 138/1350 (10.2) | 57/588 (9.7) | |
| Unemployed | 135/999 (13.5) | 154/1350 (11.4) | 67/588 (11.4) | |
| Disease; n (%) | ||||
| Ulcerative colitis | 581/993 (58.5) | 860/1348 (63.8) | 334/586 (57.0) | p = 0.0046 |
| Crohn's disease | 412/993 (41.5) | 488/1348 (36.2) | 252/586 (43.0) | |
| Medical history (years); n (%) | ||||
| ≤ 5.00 | 323/990 (32.6) | 463/1326 (34.9) | 173/587 (29.5) | p > 0.05 |
| 5.01–10.00 | 215/990 (21.7) | 297/1326 (22.4) | 125/587 (21.3) | |
| 10.01–15.00 | 144/990 (14.6) | 191/1326 (14.4) | 87/587 (14.8) | |
| 15.01–20.00 | 119/990 (12.0) | 127/1326 (9.6) | 66/587 (11.2) | |
| ≥ 20.01 | 189/990 (19.1) | 248/1326 (18.7) | 136/587 (23.1) | |
| Surgical history (times); n (%) | ||||
| ≤ 0 | 670/947 (70.8) | 959/1286 (74.6) | 395/564 (70.0) | p = 0.0180 |
| 1 | 112/947 (11.8) | 157/1286 (12.2) | 78/564 (13.8) | |
| 2 | 82/947 (8.7) | 81/1286 (6.3) | 32/564 (5.7) | |
| ≥ 3 | 83/947 (8.8) | 89/1286 (6.9) | 59/564 (10.5) | |
| Stoma (artificial anus); n (%) | 52/986 (5.3) | 52/1331 (3.9) | 36/584 (6.2) | p = 0.0759 |
| Self‐assessment of disease activity using VAS; n (%) | ||||
| Remission (VAS 1) | 372/992 (37.5) | 513/1350 (38.0) | 214/591 (36.2) | p > 0.05 |
| Mild (VAS 2–4) | 352/992 (35.5) | 466/1350 (34.5) | 225/591 (38.0) | |
| Moderate (VAS 5–7) | 204/992 (20.6) | 266/1350 (19.7) | 102/591 (17.2) | |
| Severe (VAS 8–10) | 64/992 (6.5) | 105/1350 (7.8) | 50/591 (8.5) | |
| Visiting a hospital near home for treatment of ulcerative colitis or Crohn's disease; n (%) | 84/989 (8.5) | 99/1337 (7.4) | 24/585 (4.1) | p = 0.0040 |
| Residence and hospital are in different prefectures; n (%) | 115/1003 (11.5) | 74/1362 (5.4) | 45/593 (7.6) | p < 0.0001 |
| Usual interval between visits to the hospital (months); n (%) | ||||
| ≤ 1 | 274/989 (27.7) | 335/1344 (24.9) | 152/584 (26.0) | p > 0.05 |
| 2–3 | 708/989 (71.6) | 1003/1344 (74.6) | 430/584 (73.6) | |
| ≥ 4 | 7/989 (0.7) | 6/1344 (0.5) | 2/584 (0.3) | |
| Time from home to hospital (hours); n (%) | ||||
| ≤ 0.5 | 285/991 (28.8) | 887/1344 (66.0) | 296/588 (50.3) | p < 0.0001 |
| 1–2 | 659/991 (66.5) | 444/1344 (33.0) | 291/588 (49.5) | |
| ≥ 3 | 47/991 (4.7) | 13/1344 (1.0) | 1/588 (0.2) | |
| Usual means of commuting to the hospital; n (%) b | ||||
| Walking or Bicycling | 38/994 (3.8) | 133/1350 (9.9) | 61/591 (10.3) | p < 0.0001 |
| Car | 821/994 (82.6) | 990/1350 (73.3) | 314/591 (53.1) | p < 0.0001 |
| Bus | 68/994 (6.8) | 147/1350 (10.9) | 93/591 (15.7) | p < 0.0001 |
| Train | 170/994 (17.1) | 219/1350 (16.2) | 200/591 (33.8) | p < 0.0001 |
| Others | 13/938 (1.4) | 30/1245 (2.4) | 37/565 (6.6) | p < 0.0001 |
Note: Group A: MPSPR with ≤ 150 000 people. Group B: MPSPR with 150 001–1 000 000 people. Group C: MPSPR with ≥ 1 000 001 people.
Abbreviations: IQR, interquartile range; MPSPR, Municipal population size at the place of residence; VAS, Visual Analog Scale.
Missing values for each item were excluded from the denominator.
There is duplication.
TABLE 2.
Current treatment status for inflammatory bowel disease in the three groups divided by MPSPR.
| Current treatment status a | Group A n = 1003 b n (%) | Group B n = 1362 b n (%) | Group C n = 593 b n (%) | Pearson (p) |
|---|---|---|---|---|
| 5‐Aminosalicylic acid preparations | 784/990 (79.2) | 1080/1351 (79.9) | 466/591 (78.9) | p > 0.05 |
| Pentasa suppositories | 106/990 (10.7) | 174/1351 (12.9) | 76/591 (12.9) | p > 0.05 |
| SASP suppositories | 5/990 (0.5) | 8/1351 (0.6) | 3/591 (0.5) | p > 0.05 |
| 5‐ASA enema | 41/990 (4.1) | 56/1351 (4.2) | 34/591 (5.8) | p > 0.05 |
| Oral steroid | 70/990 (7.1) | 95/1351 (7.0) | 35/591 (5.9) | p > 0.05 |
| Parenteral steroid | 14/990 (1.4) | 16/1351 (1.2) | 5/591 (0.9) | p > 0.05 |
| Steroid suppositories | 6/990 (0.6) | 16/1351 (1.2) | 0/591 (0.0) | p = 0.0169 |
| Steroid enema (STERONEMA) | 4/990 (0.4) | 3/1351 (0.2) | 2/591 (0.3) | p > 0.05 |
| Steroid enema (PREDONEMA) | 6/990 (0.6) | 9/1351 (0.7) | 3/591 (0.5) | p > 0.05 |
| Oral Budesonide | 17/933 (1.8) | 20/1246 (1.6) | 11/566 (1.9) | p > 0.05 |
| Budesonide enema | 74/990 (7.5) | 90/1351 (6.7) | 28/591 (4.7) | p > 0.05 |
| Thiopurine | 326/990 (32.9) | 406/1351 (30.1) | 196/591 (33.2) | p > 0.05 |
| Tacrolimus | 12/990 (1.2) | 12/1351 (0.9) | 3/591 (0.5) | p > 0.05 |
| Infliximab | 212/990 (21.4) | 219/1351 (16.2) | 131/591 (22.2) | p = 0.0008 |
| Adalimumab | 143/990 (14.4) | 167/1351 (12.4) | 65/591 (11.0) | p > 0.05 |
| Golimumab | 19/990 (1.9) | 34/1351 (2.5) | 14/591 (2.4) | p > 0.05 |
| Ustekinumab | 82/990 (8.3) | 103/1351 (7.6) | 60/591 (10.2) | p > 0.05 |
| Vedolizumab | 62/990 (6.3) | 72/1351 (5.3) | 42/591 (7.1) | p > 0.05 |
| Tofacitinib | 20/990 (2.0) | 30/1351 (2.2) | 20/591 (3.4) | p > 0.05 |
| Granulocyte apheresis therapy | 15/990 (1.5) | 10/1351 (0.7) | 6/591 (1.0) | p > 0.05 |
| Nutritional therapy | 160/933 (17.2) | 169/1246 (13.6) | 66/565 (11.7) | p = 0.0074 |
Note: Group A: MPSPR with ≤ 150 000 people. Group B: MPSPR with 150 001–1 000 000 people. Group C: MPSPR with ≥ 1 000 001 people.
Abbreviation: MPSPR, Municipal population size at the place of residence.
There is duplication.
Missing values for each item were excluded from the denominator.
3.4. Content of Anxiety in the Three Groups Divided by MPSPR
We compared the content of anxiety in the three groups divided by MPSPR (Figure 3). “I am worried about visiting the hospital because I have to use public transportation” was significantly higher at 22.6% in Group C, compared to 10.9% in Group A and 11.6% in Group B. On the contrary, “The hospital is located far away, and I am worried about traveling to a city with prevalence of COVID‐19” was significantly higher at 26.5% in Group A, compared to 6.6% in Group B and 5.1% in Group C. Additionally, “I have a surplus of oral medication or can get a prescription by phone, but I feel uneasy when I have to visit a doctor for an intravenous drip or injection” was significantly higher at 11.7% in Group A, compared to 7.4% in Group B and 9.0% in Group C.
FIGURE 3.
Content of anxiety in the three groups divided by municipal population size at the place of residence. Content of current or past anxiety during the COVID‐19 pandemic in three groups divided by MPSPR. (a–m) show the content of anxiety. (c) was significantly higher in Group A compared to the other two groups. On the contrary, (d) and (b) were significantly higher in Group C compared to the other two groups. Group A: MPSPR with ≤ 150 000 people. Group B: MPSPR with 150 001–1 000 000 people. Group C: MPSPR with ≥ 1 000 001 people. MPSPR, Municipal population size at the place of residence.
3.5. Usual Hospital Attendance Status in the Three Groups Divided by MPSPR
We analyzed the regular hospital attendance status of Groups A, B, and C. Although there was no difference in the usual interval between visits to the hospital among the three groups, in Group A, the time from home to hospital was significantly longer than in the other two groups, with more than 70% of the cases taking an hour or more.
Usual means of commuting to the hospital also significantly differed among the three groups, with 82.6% of the patients in Group A using a car, and 49.5% of those in Group C using public transportation such as buses and trains.
3.6. Changes in Hospital Visits, Endoscopic Examination, and IBD Treatments During the COVID‐19 Pandemic
We examined the changes in medical visits, endoscopic examination, and IBD treatments during the COVID‐19 pandemic. In the overall analysis, approximately 10% of the patients postponed a medical visit, 20% postponed or canceled an endoscopic examination, and 3% reduced or discontinued therapeutic drugs. These items were examined by dividing the population into three groups divided by MPSPR, but there were no significant differences among the three groups (Figure S4).
3.7. IBD Drug Information During the COVID‐19 Pandemic
Participants received information about the increased risk of SARS‐CoV‐2 infection due to IBD medications through several sources (Figure 4a–c). Concerning steroids and immunomodulators or oral tacrolimus, the proportion of individuals obtaining information from “Family or acquaintances (non‐medical personnel)” was significantly higher in Group C than in the other two groups (p = 0.0343), although the differences were small. Regarding the information source for JAK inhibitors or biological agents, compared to steroids and immunomodulators or oral tacrolimus, the proportion of individuals obtaining information from their “Primary doctor” was higher. When comparing the three groups divided by MPSPR with respect to JAK inhibitors or biological agents, Group C had a lower proportion of “Only my own thoughts” and higher proportion of “Primary doctor”, while Group A had a higher proportion of “Magazines” and “Internet”.
FIGURE 4.
Source of information on risk of SARS‐CoV‐2 infection related to IBD medications in the three groups divided by municipal population size at the place of residence. Figure 4 shows the source of information on steroids (a), immunomodulators or oral tacrolimus (b), and JAK inhibitors or biological agents (c) during the COVID‐19 pandemic in the three groups divided by MPSPR. (a–i) show the following Source of information: (a) Only my own thoughts; (b) Family or acquaintances (medical personnel); (c) Family or acquaintances (non‐medical personnel); (d) Primary doctor; (e) Patient groups; (f) Magazines; (g) Newspapers; (h) Internet; and (i) Television. Group A had a higher proportion of (a) and (d), while Group C had a higher proportion of (f) and (h). Group A: MPSPR with ≤ 150 000 people. Group B: MPSPR with 150 001–1 000 000 people. Group C: MPSPR with ≥ 1000 001 people. MPSPR, Municipal population size at the place of residence; VAS, Visual analog scale.
4. Discussion
In this post hoc analysis of J‐DESIRE, we investigated the relationship between MPSPR and anxiety in Japanese patients with IBD during the COVID‐19 pandemic. First, the VAS score of anxiety was high in municipalities with large or small populations and low in municipalities with intermediate populations. Next, the mean VAS score for anxiety was higher than the overall mean VAS score in municipalities with large and small populations, while it was lower in municipalities with medium populations. Based on these findings, we defined three groups according to MPSPR: Group A (≤ 150 000), Group B (150 001–1 000 000), and Group C (≥ 1 000 001). The three groups divided by MPSPR had different background factors, anxiety details, and sources of information regarding therapeutic drugs. In particular, the three groups differed significantly in the usual interval between visits to the hospital, the time spent traveling from home to the hospital, and their usual means of commuting to the hospital, which may have contributed to the elevated anxiety levels. We considered that these differences led to differences in the degree and content of anxiety. There have been many reports in the past about regional differences in medical care, but most of them are at the local or prefectural level, and there are almost no reports at the nationwide municipal level in Japan. To our knowledge, this is the first study to demonstrate that MPSPR contributed to anxiety in patients with IBD during the COVID‐19 pandemic.
Over the past few decades, Japan's population and industry have moved to urban areas, and rural areas have become depopulated and aged. As a result, rural areas have limited access to social determinants of health such as education, employment, housing, information, and health care [15, 16, 17]. Additionally, in non‐urban areas of Japan, there are few doctors and medical staff who are experts in treating IBD. Cao et al. [18] reported that living in an urban area and having a stable family income were protective factors against anxiety during the COVID‐19 outbreak. Furthermore, social support was negatively correlated with anxiety levels. Therefore, in the low MPSPR group, anxiety may have been caused by limited access to social determinants of health and a lack of social support. Additionally, many studies have reported that population density is associated with the risk of SARS‐CoV‐2 infection, and that travel and mobility increase the risk of infection [19, 20, 21, 22]. Similar to other countries, movement to urban areas had been restricted in Japan. This situation is likely to have increased anxiety not only for people living in urban areas but also for those in rural areas who need to travel to urban centers for specialized care, especially during declaration of a state of emergency.
To investigate the causes of this unique relationship between MPSPR and anxiety, we divided the population into three groups by MPSPR and examined the background factors. In Group A, hospital visit times were long and a higher proportion of patients visited hospitals in other prefectures compared to the other two groups. In Group C, the proportion of patients who visited the hospital by public transportation was higher than in the other two groups. In the context of anxiety, the proportion of anxiety regarding moving to the city was higher in Group A, while the proportion of anxiety regarding using public transportation was higher in Group C.
Next, we examined the status of medical visits, endoscopic examination, and IBD treatments during the COVID‐19 pandemic. In the J‐DESIRE study, participants' self‐assessment of disease activity using a VAS was as follows: remission (VAS 1) in 37.7%, mild (VAS 2–4) in 35.6%, moderate (VAS 5–7) in 19.3%, and severe (VAS 8–10) in 7.3%. It is surprising that the results for Group A, with many patients attending distant hospitals, were similar to those for the other two groups. Many countries have reported medication adherence rates among patients with IBD during the pandemic, but results have varied widely by country, research period, and medication category [23]. A study showed medication adherence was high in Japan [24]. In this post hoc analysis of J‐DESIRE, patients with IBD attended hospital visits and received treatment as scheduled. This outcome contrasts with certain studies conducted in other countries, where anxiety was a stronger barrier to healthcare access. Cultural attitudes toward medical advice and the healthcare system may have played a role in maintaining medication adherence and clinic visits among Japanese patients. In addition, in some Japanese regions, there are fewer physicians and medical staff experienced in IBD treatment, leading many patients to seek care at specialized core hospitals. As a result, most patients may have continued visiting hospitals for extended periods despite the fear of contracting COVID‐19. However, further research is needed on the factors associated with medication adherence in situations such as the COVID‐19 pandemic.
Regarding the increased risk of SARS‐CoV‐2 infection related to JAK inhibitors or biological agents, Group A obtained more information from magazines and the Internet than the other two groups. The anxiety of patients with IBD during the pandemic has been associated with the difficulty in accessing risk information [10]. Generally, searching for health information only through unofficial channels has been less likely to reduce concerns regarding the impact of COVID‐19 on health [25]. The Japan IBD Task Force provided COVID‐19‐related information to doctors and patients with IBD early in the pandemic [26, 27]. Nevertheless, patients do not always search through official websites. Taken together, it is necessary for the attending physician to proactively convey correct information to the patient.
This study has several limitations. First, the timing of the questionnaires was different in each group. The J‐DESIRE study found that anxiety increased approximately 1 month after the number of Japanese people infected with SARS‐CoV‐2 increased. Therefore, differences in the timing of collecting questionnaires may have led to differences in the level of anxiety. Second, we analyzed only 524 municipalities, whereas there are approximately 1700 municipalities in Japan, that is, we did not collect information from all municipalities in Japan. Third, there was a bias in the number of cases among the municipalities investigated. Fourth, this study was a cross‐sectional study, and it was not possible to evaluate changes in anxiety over time for each patient. Fifth, our use of a 10‐point VAS for anxiety, rather than a validated clinical instrument, may limit the generalizability of our conclusions regarding clinical thresholds of anxiety.
Our findings suggest that region‐specific strategies may help reduce anxiety in patients with IBD during future pandemics or similar disruptive public health events. For example, proactive communication, flexible prescribing protocols, and telehealth could enhance access to medical advice, reduce travel burdens, and ensure the accurate transfer of information.
In conclusion, we investigated the association between anxiety in patients with IBD and MPSPR nationwide during the COVID‐19 pandemic in Japan. The results obtained in this analysis are useful not only in special situations such as the COVID‐19 pandemic, but also for considering regional differences in medical care.
Ethics Statement
This study protocol was approved by the institutional review board of Sapporo Medical University and registered publicly on the UMIN registration (No. UMIN000041191).
Conflicts of Interest
Takayuki Matsumoto reports receiving personal fees from Janssen, Tanabe‐Mitsubishi Pharmaceutical, EA Pharma, Takeda Pharmaceutical, and scholarship grants from Nippon Kayaku, Tanabe‐Mitsubishi Pharmaceutical. Minoru Matsuura reports receiving personal fees from AbbVie GK, Janssen Pharmaceutical K.K., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Mochida Pharmaceutical Co. Ltd., JIMRO Co. Ltd., Kissei Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Zeria Pharmaceutical Co. Ltd., Viatris Inc., Sandoz K.K., and EA pharma Co. Ltd. Katsuyoshi Matsuoka reports receiving personal fees from Mitsubishi Tanabe Pharma, AbbVie, Takeda Pharmaceutical, EA Pharma, Janssen Pharmaceutical, Pfizer, Mochida Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Kissei Pharmaceutical Co. Ltd., Gilead Sciences Inc., Eli Lilly, Nippon Kayaku Co. Ltd., Celltrion Healthcare, research grants from Janssen Pharmaceutical, and scholarship grants from Mitsubishi Tanabe Pharma, AbbVie, EA Pharma, Mochida Pharmaceutical, JIMRO, Nippon Kayaku Co. Ltd. Shunji Ishihara reports receiving personal fees from Takeda Pharmaceutical Co. Ltd. Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Nippon Kayaku Co. Ltd., Mochida Pharmaceutical Co., Zeria Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co. Ltd., JIMRO Co. Ltd., EA Pharma Co. Ltd., AbbVie GK, KISSEI Pharmaceutical Co., KYORIN Pharmaceutical Co. Ltd., Pfizer Japan Inc., and Miyarisan Pharmaceutical Co. Fumihito Hirai reports receiving personal fees from AbbVie GK, EA Pharma Co. Ltd., Janssen Pharmaceutical K.K., Mochida Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co., Takeda Pharmaceutical Co. Ltd., research grants from Eli Lily Japan K.K., Janssen Pharmaceutical K.K., AbbVie GK., and scholarship grants from AbbVie GK, EA Pharma Co. Ltd., Otsuka Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Co. Ken Takeuchi reports receiving personal fees from Mochida, AbbVie, Janssen pharma, Pfizer, and EA Pharma, and research grants from AbbVie, Takeda, Eli Lilly, Celgene, Shin Nippon Biomedical Laboratories, EA Pharma, Astra Zeneca, and Janssen pharma. Nobuhiro Ueno reports receiving grants from Pfizer Inc. Makoto Naganuma reports receiving research grant fees from Mitsubishi Tanabe Pharma Corporation, AbbVie GK, Kyorin Pharmaceutical Co. Ltd., Alfresa Pharma Corporation and lecture fees from Tanabe Pharma Corporation, AbbVie GK, Takeda Pharmaceutical Co. Ltd., JIMRO Co. Ltd., Janssen Pharmaceutical K.K., Gilead Sciences Inc. EA Pharma Co. Ltd., and Mochida Pharmaceutical Co. Ltd. Kenji Watanabe reports receiving personal fees from, AbbVie Japan Co. Ltd., EA Pharma Co. Ltd., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., and Kissei Pharmaceutical Co. Ltd., research grants from EA Pharma Co. Ltd., Takeda Pharmaceutical Co. Ltd., and EP‐CRSU Co. Ltd., scholarship grants from AbbVie Japan Co. Ltd., EA Pharma Co. Ltd., Mitsubishi Tanabe Pharma Corporation, JIMRO Co. Ltd., and Nippon Kayaku Co. Ltd., and endowed chair from AbbVie Japan Co. Ltd., EA Pharma Co. Ltd., Mitsubishi Tanabe Pharma Corporation, ZERIA Pharmaceutical Co. Ltd., JIMRO Co. Ltd., Otsuka Pharmaceutical Factory Inc., Asahi Kasei Medical Co. Ltd., and Mochida Pharmaceutical Co. Ltd. Satoshi Motoya reports receiving personal fees from AbbVie GK, Mitsubishi‐Tanabe Pharma Corporation, Mochida Pharma Corporation, Takeda Pharmaceutical Corporation, and Janssen Pharmaceutical K.K., and scholarship grants from AbbVie GK, Eli Lilly Japan K.K., and Janssen Pharmaceutical K.K. Atsuo Maemoto reports receiving research grants from Gilead Sciences Inc., Janssen Pharmaceutical K.K., Eli Lilly Japan K.K., Takeda Pharmaceutica Company, Pfizer R&D Japan G.K. Masayuki Saruta reports receiving personal fees from AbbVie GK, Janssen Pharmaceutical K.K., Mitsubishi Tanabe Pharma Co. Ltd., Takeda Pharmaceutical Co. Ltd., EA Pharma Co. Ltd., Kissei Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., Viatris Pharmaceutical Co. Ltd., Nobelpharma Co. Ltd., and Gilead Sciences K.K., research grants from AbbVie GK, CMIC CMO Co. Ltd., PPD‐SNBL K.K., and scholarship grants from AbbVie GK, Zeria Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., and Kissei Pharmaceutical Co. Ltd. Hiroki Tanaka reports receiving personal fees from JIMRO Co. Ltd., AbbVie GK, EA Pharma Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd., Kissei Pharmaceutical Co. Ltd., Eisai Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Janssen Pharmaceutical K.K., Nikkiso Co. Ltd., Takeda Pharmaceutical, and research grants from AbbVie GK, Janssen Pharmaceutical K.K., EA Pharma, Takeda Pharmaceutical. Tadakazu Hisamatsu reports receiving personal fees from EA pharma Co. Ltd., AbbVie GK, Janssen Pharmaceutical K.K., Pfizer Inc., Nichi‐Iko Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Kyorin Pharmaceutical Co. Ltd., JIMRO Co., Mochida Pharmaceutical Co. Ltd., Eli Lilly, Gilead Sciences, Bristol Myers Squibb, and Takeda Pharmaceutical Co. Ltd., research grants from Kissei Pharmaceutical Co. Ltd. and EA pharma Co. Ltd., and scholarship grants from Mitsubishi Tanabe Pharma Corporation, EA pharma Co. Ltd., AbbVie GK, JIMRO Co. Ltd., Zeria Pharmaceutical Co. Ltd., Kyorin Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Takeda Pharmaceutical Co. Ltd., Pfizer Inc., Boston Scientific Corporation, and Mochida Pharmaceutical Co. Ltd. Hiroshi Nakase reports receiving personal fees from Mitsubishi Tanabe Pharma Corporation, Abbvie Inc., Janssen Pharmaceutical K.K, VIATRIS Inc., Pfizer Japan Inc., Takeda Pharmaceutical Co. Ltd., EA Pharma Co. Ltd., Mochida Pharmaceutical Co. Ltd., Gilead Sciences Inc., Daiichi Sankyo Co. Ltd., and research grants from Hoya Group Pentax Medical, Abbvie Inc., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co. Ltd., AYUMI Pharmaceutical Corporation, and scholarship grants from Abbvie Inc., Otsuka Pharmaceutical Co. Ltd., EA Pharma Co. Ltd., TAIHO Pharmaceutical Co. Ltd., Nippon Kayaku Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Co. Ltd. He was endowed chair by MIYARISAN Pharmaceutical Co., JIMRO Co. Ltd., KYORIN Pharmaceutical Co. Ltd., Mochida Pharmaceutical Co. Ltd.
Supporting information
Table S1. Overall participants’ demographic characteristics at baseline.
Table S2. Overall current treatment status for inflammatory bowel disease.
Table S3. Municipality‐wise population and number of patients.
Figure S1. Relationship between municipal population density at place of residence and anxiety.
Figure S2. Timing of questionnaire collection in the three groups divided by MPSPR. This figure shows the monthly percentage of collected questionnaires in each of the three groups divided by MPSPR. This study period spanned between March 2020 and June 2021. There was variation in the timing of questionnaire collection among the three groups.
Figure S3. Age comparison of the three groups divided by MPSPR. This figure shows the age distribution of the three groups divided by MPSPR. The green scale bar shows the frequency distribution of each group. Group C was significantly younger than Group B (p = 0.0110).
Figure S4. Changes in hospital visits, endoscopic examination, and IBD treatments during the COVID‐19 pandemic in the three groups divided by MPSPR. This figure shows the changes in hospital visits, endoscopic examination, and IBD treatments during the COVID‐19 pandemic in the three groups divided by MPSPR. There were no significant differences between the three groups.
Acknowledgments
The authors are grateful to the entire The Japan COVID‐19 Survey and the Questionnaire for Inflammatory Bowel Disease (J‐DESIRE) Group. Sae Ohwada (Sapporo Medical University School of Medicine), Takehiro Hirano (Sapporo Medical University School of Medicine), Yoshihiro Yokoyama (Sapporo Medical University School of Medicine), Tsukasa Yamakawa (Sapporo Medical University School of Medicine), Yuki Hayashi (Sapporo Medical University School of Medicine), Tadashi Ichimiya (Sapporo Medical University School of Medicine), Tomoe Kazama (Sapporo Medical University School of Medicine), Daisuke Hirayama (Sapporo Medical University School of Medicine), Ayuko Hazumi (Sapporo Medical University Hospital), Ayumi Kadoya (Sapporo Medical University Hospital), Saki Asakura (Sapporo Medical University Hospital), Naomi Ebisawa (Sapporo Medical University Hospital), Shunichi Yanai (Iwate Medical University), Daisuke Saito (Kyorin University School of Medicine), Shinichiro Shinzaki (Osaka University Graduate School of Medicine), Akihiro Yamada (Toho University Sakura Medical Center), Mitsuo Nagasaka (Fujita Health University School of Medicine), Kousaku Kawashima (Shimane University), Nobuaki Kuno (Fukuoka University), Yoshihiro Shimoyama (Tsujinaka Hospital Kashiwanoha), Ken Sugimoto (Hamamatsu University School of Medicine), Nobufumi Uchima (Urasoe General Hospital), Mikihiro Fujiya (Asahikawa Medical University), Norimasa Fukata (Kansai Medical University), Yoko Yokoyama (Hyogo Medical University), Atsushi Masamune (Tohoku University Hospital), Yukinori Sameshima (Sameshima Hospital), Ryosuke Kiyomori (Matsuyama Red Cross Hospital), Tomoki Inaba (Kagawa Prefectural Central Hospital), Takahiro Ito (Sapporo Higashi Tokushukai Hospital), Hirotake Sakuraba (Hirosaki University Graduate School of Medicine), Takahiko Toyonaga (The Jikei University School of Medicine), Takanao Tanaka (Dokkyo Medical University), Akihiro Koga (Fukuoka University Chikushi Hospital), Masanao Nasuno (Sapporo IBD Clinic), Yuzo Kawata (Niigata University), Sakiko Hiraoka (Okayama University Graduate School of Medicine), Motohiro Esaki (Saga University), Ryota Hokari (National Defense Medical College), and Yuki Yoshino (Tohoku Medical and Pharmaceutical University). We would like to thank Editage (www.editage.com) for English language editing. This work was supported by MHLW Research on Emerging and Re‐emerging Infectious Diseases and Immunization (Program Grant Number JPMH21HA2011, JPMH23HA2011 and JPMH24HA2015).
Wagatsuma K., Nojima M., Matsumoto T., et al., “Post Hoc Analysis of Anxiety and Behavioral Changes in Japanese Patients With Inflammatory Bowel Disease due to the COVID‐19 Pandemic: Relationship Between Municipal Population at the Place of Residence and Anxiety,” JGH Open 9, no. 7 (2025): e70209, 10.1002/jgh3.70209.
Funding: This work was supported by the Health and Labour Sciences Research Grants for research on intractable diseases from the Ministry of Health, Labour and Welfare (MHLW) of Japan (Investigation and Research for intractable Inflammatory Bowel Disease), 20FC1037; MHLW Research on Emerging and Re‐emerging Infectious Diseases and Immunization, JPMH21HA2011, JPMH23HA2011, JPMH24HA2015.
A complete list of the J‐DESIRE Group is provided in the Acknowledgments.
Contributor Information
Hiroshi Nakase, Email: hiropynakase@gmail.com.
J‐DESIRE Group:
Sae Ohwada, Takehiro Hirano, Yoshihiro Yokoyama, Tsukasa Yamakawa, Yuki Hayashi, Tadashi Ichimiya, Tomoe Kazama, Daisuke Hirayama, Ayuko Hazumi, Ayumi Kadoya, Saki Asakura, Naomi Ebisawa, Shunichi Yanai, Daisuke Saito, Shinichiro Shinzaki, Akihiro Yamada, Mitsuo Nagasaka, Kousaku Kawashima, Nobuaki Kuno, Yoshihiro Shimoyama, Ken Sugimoto, Nobufumi Uchima, Mikihiro Fujiya, Norimasa Fukata, Yoko Yokoyama, Atsushi Masamune, Yukinori Sameshima, Ryosuke Kiyomori, Tomoki Inaba, Takahiro Ito, Hirotake Sakuraba, Takahiko Toyonaga, Takanao Tanaka, Akihiro Koga, Masanao Nasuno, Yuzo Kawata, Sakiko Hiraoka, Motohiro Esaki, Ryota Hokari, and Yuki Yoshino
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Table S1. Overall participants’ demographic characteristics at baseline.
Table S2. Overall current treatment status for inflammatory bowel disease.
Table S3. Municipality‐wise population and number of patients.
Figure S1. Relationship between municipal population density at place of residence and anxiety.
Figure S2. Timing of questionnaire collection in the three groups divided by MPSPR. This figure shows the monthly percentage of collected questionnaires in each of the three groups divided by MPSPR. This study period spanned between March 2020 and June 2021. There was variation in the timing of questionnaire collection among the three groups.
Figure S3. Age comparison of the three groups divided by MPSPR. This figure shows the age distribution of the three groups divided by MPSPR. The green scale bar shows the frequency distribution of each group. Group C was significantly younger than Group B (p = 0.0110).
Figure S4. Changes in hospital visits, endoscopic examination, and IBD treatments during the COVID‐19 pandemic in the three groups divided by MPSPR. This figure shows the changes in hospital visits, endoscopic examination, and IBD treatments during the COVID‐19 pandemic in the three groups divided by MPSPR. There were no significant differences between the three groups.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.