Trends in hospital admissions and prescribing due to diseases of the digestive system in England and Wales between 1999 and 2019: An ecological study

This study aimed to investigate the trends in diseases of the digestive system hospital admissions (DDSHA) in England and Wales between (1999–2019). Secondary objectives were to investigate the type of admission and medication prescribing related to the digestive system in England. This is an ecological study using data from the Hospital Episode Statistics (HES) database and the Patient Episode Database between April 1999 and March 2019. The rate of hospital admissions with 95% confidence intervals (CIs) was calculated by dividing the number of DDSHA by the mid-year population. The trend in hospital admissions was assessed using a Poisson model. Overall, the rate of DDSHA rose by 84.2% (from 2231.27 [95% CI 2227.26–2235.28] in 1999 to 4109.33 [95% CI 4104.29–4114.38] in 2019 per 100,000 persons, trend test, P < .001). The most remarkable rise in hospital admission was seen in liver diseases, followed by other diseases of intestines with 1.85-fold, and 1.59-fold, respectively. Between 2004 and 2019, the overall prescribing rate for medications related to the gastrointestinal system increased by 74.6%, and stoma care related medications prescribing rate increased by 2.25-fold, followed by drugs affecting intestinal secretions and antisecretory drugs and mucosal protectants. There was an increase in hospital admission rate due to GI diseases in the United Kingdom (UK) by 84.2% from 1999 to 2019. The most remarkable rise in the rate of hospital admissions was seen in diseases of the liver and intestine.


Introduction
Diseases of the gastrointestinal (GI) system are highly prevalent worldwide, making them a substantial burden on the healthcare system. [1]GI cancers were among the leading causes of death in the United Kingdom (UK) in 2019. [2]In addition, a large number of GI system diseases are chronic in nature, leading to a higher risk of morbidity and a worse quality of life for patients. [3]GI disorders can be life-threatening or require hospital admission, while others such as gastro-esophageal reflux disease, peptic ulcer diseases, irritable bowel diseases, anorectal disorders, and chronic liver disease are more chronic but affect the quality of life of patients, require multiple medical follow-ups, investigations, and continuous treatments, leading to a significant burden on the economic system. [4] diseases account for approximately 8 million deaths per year worldwide, and it is estimated that around 60 to 70 million Americans are affected by GI diseases annually.[5] In a recent study in the UK using a large database, Pasvol et al reported that the incidence of inflammatory bowel disease was 28.6 (28.2-28.9)per 100,000 person-years during the study period from 2000 to 2018.[6] Another study in the UK estimated that the crude incidence of liver cirrhosis was around 14.55 per 100,000 person-years, increasing from 12.05 to 16.99 per 100,000 person-years from 1992 to 2001.[7] The incidence of GI diseases, including nonalcoholic fatty liver disease, alcohol-related liver disease and intestinal diseases has risen significantly in the last few years; this was even highlighted in the report by the Office for National Statistics in the UK and by the Lancet Commission into liver disease.[8,9] The time trend of incidence and hospital admissions of GI diseases has changed over the last 30 years.12] However, these studies were mainly in the United States and focused on a certain disease.
In the last 30 years, multiple interventions and pharmacological treatments have changed the practice of treating GI diseases, including authorization of a new biological treatment for inflammatory diseases, improved hygiene, growing affluence, rapid urbanization, and many changes in lifestyle, especially in westernized countries with better access to healthcare services. [10]These measures may have directly affected the time trend in hospital admissions for GI diseases including liver disease.However, recent studies investigating this issue are limited.Hospital admission is costly and may be preventable in some cases; therefore, estimating the trend and types of these admissions may help in identifying patterns of increase and decrease and may be an initial step in identifying factors associated with these admissions.Therefore, the primary objective of this study was to investigate the trends in hospital admissions related to diseases of the digestive system in England and Wales between 1999 and 2019.Secondary objectives were to investigate the type of admission and medication prescribing related to the digestive system in England.

Data sources and study population
An observational retrospective ecological design was used to analyze data from the Hospital Episode Statistics (HES) database in England and the Patient Episode Database for Wales.[15][16][17][18][19][20][21][22][23] The 2 databases are regularly checked to ensure their validity and accuracy. [24]HES database undergoes an automated data cleaning system, and it has been tested for its internal validity. [25]Data regarding hospital admission between April 1999 and March 2019 were included.HES and patient episode database for Wales databases contain hospital admission data, outpatient clinic and emergency visits for all types of diseases of the digestive system (DDS) for patients from all age categories: below 15 years, 15 to 59 years, 60 to 74 years, and 75 years and above that occur at all National Health Service trusts.Hospital admission data recorded in HES database are further classified into several types including day case admissions, elective admissions, emergency admissions and waiting list admissions.Day case admissions include Patients who are admitted electively during the day for treatment or intervention, however, they do not require overnight stay in hospital and can be discharged.waiting list admissions include patients admitted from an elective admission list, however, the hospital where the patient should be admitted were not available, and a bed could not be booked at the time.Elective admission: where the health care provider has known about at least 24 hours in advance.Emergency admission: patients admitted to hospital for emergency intervention and care.Diseases of the digestive system hospital admissions (DDSHA) were identified using the tenth version of the International Statistical Classification of Diseases system.Data for hospital admissions in England and Wales are available from the years 1999/2000 onwards.To calculate the annual hospital admission rate for DDS, we collected mid-year population data between 1999 and 2019 from the Office for National Statistics.The digestive system related medication prescription data in England and Wales were extracted from the Prescription Cost Analysis database for the available period of 2004 to 2019.This data was estimated by the national health service Prescription Services to have around 98.5% of accuracy for patients in England and 99.2% for patients in Wales. [26]

Data analysis
Annual DDSHA rates with 95% confidence intervals (CIs) were calculated using the number of hospital admissions related to DDS divided by the mid-year population of the same year.Further stratification by age and gender and by each type of DDS were also conducted.GI related medication prescription rates were calculated using the number of GI medication prescriptions divided by the total mid-year population during the same year.A chi-square test was used to assess the difference between the hospital admission rates in 1999 and 2019.The trend in hospital admissions was assessed using a Poisson model.Pearson correlation coefficient was estimated to examine the correlation between the prescribing rate and admission rate.A 2-sided P < .05 was considered statistically significant.All analyses were performed using SPSS version 25 (IBM Corp, Armonk, NY, USA).

Funding
This study is funded by Princess Nourah bint Abdulrahman University Researchers Supporting Project number (PNURSP2024R483), Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.

Results
The  1).In the last twenty years, the most remarkable rise in the rate of hospital admission was seen in diseases of liver, followed by other diseases of intestines, other diseases of the digestive system, noninfective enteritis and colitis, and disorders of gallbladder, biliary tract and pancreas with 1.85-fold, 1.59-fold, 1.28-fold, 1.15-fold, and 1.04-fold, respectively.Furthermore, the rate of hospital admission due to diseases of appendix, diseases of esophagus, stomach and duodenum, and hernia were increased by 30.9%, 29.0%, and 22.4%, respectively (Fig. 1).

Diseases of the digestive system hospital admissions rate by gender
Females contributed to 50.1% of the total number of DDSHA accounting for 17,067,520 hospital admission episodes by a mean of 853,376 per year.DDSHA rate between females was increased by 90.2% (from 2144.43  DDSHA rates for for diseases of esophagus, stomach and duodenum, diseases of appendix, hernia, diseases of liver, and other diseases of the digestive system were higher among males compared to females (P < .05),(Figure S1, Supplemental Digital Content, http://links.lww.com/MD/M30).www.md-journal.com

Diseases of the digestive system hospital admissions rate by age group
The age group 15 to 59 years' accounted for 47.1% of the whole number of DDSHAs, followed the age group 60 to 74 years with 26  3).
DDSHAs for diseases of esophagus, stomach and duodenum, hernia, noninfective enteritis and colitis, other diseases of intestines, disorders of gallbladder, biliary tract and pancreas, and other diseases of the digestive system were seen to be directly related to age.However, hospital admissions due to diseases of liver were more prevalent among the age group: 60 to 74 years, 75 years and above, 15 to 59 years, and below 15 years, respectively, (Figure S2, Supplemental Digital Content, http://links.lww.com/MD/M31).

Other diseases of intestines
The overall annual rate for other diseases of intestines hospital admissions for diverse reasons increased by 1.59-fold (from 490.46 [95% CI 488.57-492.36] in 1999 to 1269.07 [95% CI 1266.22-1271.92] in 2019 per 100,000 persons, trend test, P < .05).The most increase in the hospital admission rate was seen in other diseases of intestine, diverticular disease of intestine, vascular disorders of intestine, and paralytic ileus and intestinal obstruction without hernia by 13.21-fold, 1.85-fold, 1.36-fold, and 1.15-fold, respectively (Fig. 4).

Diseases of liver
The overall annual rate for diseases of liver hospital admissions for diverse reasons increased by 1.85-fold (from 54.90 [95% CI 54. 26-55.54] in 1999 to 156.39 [95% CI 155.39-157.40]  in 2019 per 100,000 persons, trend test, P < .05).The most increase in the hospital admission rate was seen in liver disorders in diseases classified elsewhere, other inflammatory liver diseases, hepatic failure, not elsewhere classified, and toxic liver disease by 6.60-fold, 4.36-fold, 2.69-fold, and 2.04-fold, respectively (Fig. 5).

Diseases of esophagus, stomach and duodenum
The overall annual rate for diseases of esophagus, stomach and duodenum hospital admissions for diverse reasons increased by 29.0% (from 666.73 [95% CI 664.52-668.94] in 1999 to 860.13 [95% CI 857.78-862.47] in 2019 per 100,000 persons, trend test, P < .05).The most increase in the hospital admission rate was seen in other diseases of stomach and duodenum and disorders of esophagus in diseases classified elsewhere by 3.74fold and 2.07-fold, respectively (Fig. 6).

Disorders of gallbladder, biliary tract and pancreas
The overall annual rate for disorders of gallbladder, biliary tract and pancreas hospital admissions for diverse reasons increased by 1.04-fold (from 250.71 [95% CI 249.35-252.07] in 1999 to 512.26 [95% CI 510.45-514.08] in 2019 per 100,000 persons, trend test, P < .05).The most increase in the hospital admission rate was seen in other diseases of biliary tract, acute pancreatitis, and other diseases of gallbladder by 1.88-fold, 1.54-fold, and 1.23-fold, respectively (Fig. 7).

Other diseases of the digestive system
The overall annual rate for other diseases of the digestive system hospital admissions for diverse reasons increased by 1.28fold (from 140.42 [95% CI 139.40-141.43] in 1999 to 320.39 [95% CI 318.96-321.83] in 2019 per 100,000 persons, trend test, P < .05).The most increase in the hospital admission rate was seen in postprocedural disorders of digestive system, not elsewhere classified and other diseases of digestive system by 1.37-fold, and 1.32-fold, respectively (Fig. 8).Other diseases of the digestive system (intestinal malabsorption, intraoperative and postprocedural complications and disorders of digestive system, not elsewhere classified, other diseases of digestive system, complications of artificial openings of the digestive system, and complications of bariatric procedures)

7.5%
DDS = diseases of the digestive system, ICD = international statistical classification of diseases system.

Hospital admission stratified by type of admission.
Almost half of the reported number of admissions in the 2 medical databases were for regular admissions that involved inpatients treatment.Around on-third of the reported number was for elective admission (waiting list admission).The total annual rate for diseases of the digestive system admission, emergency admission, waiting list, and day case increased by 80.6%, 1.4%, 96.5%, and 1.62-fold, respectively (Fig. 9).The total annual number for diseases of the digestive system admission, emergency admission, waiting list, and day case increased by 1.06-fold, 15.6%, 1.24-fold, and 1.98-fold, respectively (Table 2).

Gastrointestinal diseases medications prescribing
Between 2004 and 2019, the overall prescribing rate for medications related to the gastrointestinal system increased by 74.6%, stoma care related medications prescribing rate increased by  2.25-fold, followed by drugs affecting intestinal secretions and antisecretory drugs and mucosal protectants which increased by 1.84-fold and 1.39-fold, respectively (Table 3).

Correlation between gastrointestinal diseases medications prescribing and its associated admission rate.
When we investigated the correlation between  GI diseases medications prescribing and its associated admission rate, the results showed a very strong positive correlation between GI diseases medications prescribing and its associated admission rate (r: 0.961; P < .001).

Discussion
The study found an increase in the overall annual number of DDSHA from 1163,388 in 1999 to 2442,581 in 2019.Previous studies investigating the trend in admissions for GI diseases in the UK are limited, and most of these studies are not specific  to a certain disease.Blunt et al reported that emergency admissions in England rose by 11.8% over the 5-year period 2004/05 to 2008/09.They also reported that older people constituted the majority of these admissions. [27]In the United States, similar patterns were also reported, with non-food-borne gastroenteritis, gastro-esophageal reflux disease and irritable bowel syndrome being among the most prevalent diseases. [28]In addition, a study in Hong Kong analyzing data from the Hong Kong Hospital Authority found that the annual incidence of hospitalization for GI diseases increased from 4713 to 5241 per 100,000 discharges (incidence rate ratio = 1.004; 95% CI 1.003-1.005). [10]They also found that GI cancers, GI infections and inflammatory diseases had the highest rate, while the incidence of peptic ulcer disease declined significantly, which is also consistent with the results reported in our study and previous literature. [10]he increase in the trend of hospital admissions due to GI diseases could be attributed to multiple issues.The frailty of aging population is a major issue worldwide and is also associated with an increased risk of comorbidities and more serious diseases, which may lead to hospital admissions. [29]In addition, with more medical technologies available and awareness in the community, there could be an increase in the ability to detect and treat illness. [30]However, it is also important to notice that with recent developments in the medical system and the management of medical issues, better care for patients at the primary care level, better access to healthcare services, better health outcomes, a reduction in hospital admissions, more stable progression of diseases, and prevention of serious emergency issues may also be expected. [31]n this study, we found that diseases of the liver had the highest increase in the trend over the 20 years of the study period, with the most increase in the hospital admission rate seen in liver disorders, alcoholic liver diseases and cirrhotic liver diseases.These results were also in line with a previous study by Thomson et al using HES data in England, in which the authors reported that admissions due to liver diseases increased during the period of 1989/1990 to 2002/2003 from 24.9 to 42.4 per 100,000 in males (71%) and from 19.3 to 27.6 per 100,000 in females (43%). [32]They also reported that alcoholic liver disease was the main contributor to this increase. [32]Liver diseases (alcoholic liver and cirrhosis) are major public health issues in Westernised countries. [33]This was also reflected in our study, which showed that the trend in liver disease admissions was increasing in the last ten years (from 2009-2019) among males and people aged 15 to 59.When stratifying the data by gender, these results were also obvious and supported this finding, showing that men had a higher trend in liver disease admissions.The relationship between alcoholic liver and male gender has been proven previously in the literature, which supports the findings of our study. [34,35][38] The burden of NAFLD has been a major public health concern in the last years, as the disease is associated with a higher risk of cirrhosis and hepatocellular carcinoma. [36]Patients with NAFLD are also more prone to comorbidities, hospital admissions and mortality. [39,40]This could also be a reason for the rise in hospital admission which was noticed in the findings of this study.
In recent years, there has been a major shift in recommendations to use biological treatments for the management of inflammatory bowel diseases, resulting in a better prognosis and fewer relapse attacks.However, our study showed that diseases of the intestine also increased in the last years.A western, sedentary lifestyle is an important risk factor linked to the development of inflammatory diseases in developed countries.In a study using HES data in England, the authors reported that agesex standardized admission rates increased from 76.5 to 202.9 per 100,000 (P < .001)and from 69.5 to 149.5 per 100,000 (P < .001)for Crohn's disease and ulcerative colitis, respectively, between 2003/2004 and 2012/2013.Our results were in line with these results, with similar results also reported in the United States. [41]ur study also demonstrated an increase in the trend of esophageal, stomach, and duodenal diseases hospital admissions.These results could be explained by the fact that even though there has been a major reduction in the incidence of peptic ulcer diseases in England mainly due to the eradication of Helicobacter pylori, [42]  there has been more ingestion of nonsteroidal anti-inflammatory inhibitors, cyclooxygenase-2 inhibitors and Selective serotonin reuptake inhibitors, and cases of osteoarthritis and inflammatory diseases, which are well-known risk factors for the development of peptic ulcer diseases and dyspepsia. [43]This was even highlighted in the results of this study as it showed a large proportion of the increase in the prescribing trend of GI medications was reported in the antisecretory medications.Many factors play a vital role in the process of triggering GI tract diseases, including eating a low fiber diet, not getting enough exercise, eating large amounts of dairy products, and stress. [44,45]At the same time, different methods can be implemented to decrease the risk of developing common digestive diseases, such as avoiding eating foods that contain saturated fats, following a healthy diet, exercise, not delaying defecation, and avoiding excessive intake of medicines. [46]I medications are among the most common prescribed medication in the UK, and the majority of the use of this class of medications fall into the antisecretory drugs.This was also highlighted in this study.Gastritis, peptic ulcer diseases are among the comments causes of primary care visits in the UK and this may explain this finding.
The results of this study may help to guide healthcare professionals and policy makers in understanding the trend in hospital admissions for GI diseases in the last years.The increase in the trend of hospital admissions due to certain diseases, such as liver and intestine diseases compared to other infectious diseases, such as Helicobacter pylori (H.Pylori), may reflect the actual lifestyle of the community, and it may also reflect the improvement in early identification in the healthcare system.Investigating factors associated with the increase in the rate of liver diseases and intestinal diseases is important and may help to achieve improvements in emergency department care for patients with and without GI diseases.

Strengths and limitations
To the best of our knowledge, this is the first study to explore trends in the rates of DDSHA in England and Wales without restricting the study to specific inclusion/exclusion criteria.Hospital admission rates for all types of DDSHA were stratified by age and gender, giving a comprehensive description of the hospitalisation profile for this group of patients over 20 years period.However, this study has some limitations.This was an ecological study, and due to the nature of data available publicly from these 2 medical databases we were unable to identify patient-level factors such as comorbidities, polypharmacy, that may impact DDSHA.In this study we did not have the capacity to explain the trends in disease prevalence and hospital admissions due to lack of population level data (which restricted our ability to adjust for important confounders) and primary care diagnosis data, however, future research using primary care data in the UK such as the Clinical Practice Research Datalink and The Health Improvement Network database may help in investigating such outcomes.Moreover, ecological studies cannot establish causality.

Conclusion
There was an increase in hospital admission rate due to GI diseases in the UK by 84.2% from 1999 to 2019.The most remarkable rise in the rate of hospital admissions was seen in diseases of the liver and intestine.

Figure 1 .
Figure 1.Hospital admission rates due to DDS in England and Wales stratified by type between 1999 and 2019.DDS = diseases of the digestive system.

Figure 2 .
Figure 2. Rates of hospital admission for all DDS in England and Wales stratified by gender.DDS = diseases of the digestive system.

Figure 3 .
Figure 3.Rates of hospital admission for all DDS in England and Wales stratified by age group.DDS = diseases of the digestive system.

Figure 4 .
Figure 4. Hospital admission rates due to other diseases of intestines in England and Wales stratified by type between 1999 and 2019.

Figure 5 .
Figure 5. Hospital admission rates due to diseases of liver in England and Wales stratified by type between.

Figure 6 .
Figure 6.Hospital admission rates due to diseases of esophagus, stomach and duodenum in England and Wales stratified by type between 1999 and 2019.

Figure 7 .
Figure 7. Hospital admission rates due to disorders of gallbladder, biliary tract and pancreas in England and Wales stratified by type between 1999 and 2019.

Figure 8 .
Figure 8. Hospital admission rates due to other diseases of the digestive system in England and Wales stratified by type between 1999 and 2019.

Figure 9 .
Figure 9. Hospital admission rates due to diseases of the digestive system in England and Wales stratified by admission type between 1999 and 2019.

Table 1
Percentage of DDS admission from total number of admissions per ICD code.

Table 2
Number of reported hospital admissions stratified by type of admissions.