Global, regional, and national burdens of pancreatitis in adults aged ≥65 years from 1992 to 2021: A trends analysis using data from the 2021 Global Burden of Disease Study.

Hang Qian: Supervision, Software, Formal analysis. Weifeng Shang: Methodology, Investigation, Formal analysis. Sheng Zhang: Project administration, Methodology, Formal analysis. Xiaojun Pan: Software, Resources. Sisi Huang: Data curation, Conceptualization. Hui Li: Visualization, Investigation. Zhenliang Wen: Visualization, Investigation. Jiao Liu: Writing – original draft, Visualization, Validation. Dechang Chen: Project administration, Funding acquisition, Conceptualization.

We obtained the data for the incidence and death numbers of pancreatitis cases from GBD 2021 using the Global Health Data Exchange results tool. We defined the study population as older adults aged ≥65 years. To summarize the age distribution of the burden of pancreatitis in older adults, patients were divided into seven groups according to age: 65–69, 70–74, 75–79, 80–84, 85–89, 90–94, and ≥95 years, respectively. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASDR) of pancreatitis in older adults were calculated using the direct method, which presumes that the rates are distributed as a weighted sum of independent Poisson random variables. [ 14 ] Both ASIR and ASDR were presented as an estimate per 100,000 people. The Sociodemographic Index (SDI) is a composite measure that reflects the combined level of health-related social and economic conditions, which is a comprehensive indicator of the development status of a country or region. It is calculated as a geometric mean of three indices, each scaled from 0 to 1: total fertility rate among women <25 years old, the average education level of individuals ≥15 years old, and the country’s lag-distributed income per capita. The 204 countries and regions were divided into five groups according to their SDI quintile: high SDI (0.806–1), high-middle SDI (0.691–0.805), middle SDI (0.609–0.690), low-middle SDI (0.456–0.608), and low SDI (0–0.455). [ 15 ] The estimated relationships between ASIR, ASDR, and SDI were evaluated using Pearson’s correlation analysis. The Joinpoint regression model is a kind of linear statistical model that has been used to evaluate trends in disease burdens across time. [ 16 ] The rates are transformed logarithmically, and standard errors are calculated using the binomial approximation. [ 16 ] By calculating the annual percentage change (APC) and the corresponding 95% confidence interval (CI), the model allows for the identification of significant changes in trends. [ 17 ] In addition, the average APC (AAPC) serves as a comprehensive measure of the trend over a specified interval, calculated as a weighted average of APCs across the different segments. An increasing trend is indicated when the AAPC estimate and the lower bound of its 95% CI are both greater than zero. Conversely, a decreasing trend is suggested when the AAPC estimate and the upper bound of its 95% CI are both less than zero. This analysis was performed using the Joinpoint Regression Program, version 4.9.1.0, provided by the U.S. National Cancer Institute (Bethesda, MD, USA). The age–period–cohort analysis is a statistical method that has been used in biological, health, and social sciences for decades. [ 18 ] As the relationship between age, period, and cohort is perfectly linear, it is statistically impossible to estimate their independent effects. [ 18 ] Here, we circumvented this issue by producing estimable age–period–cohort analysis parameters and functions without imposing arbitrary constraints on model parameters. [ 11 , 19 , 20 ] The parameters were estimated using the tool provided by the U.S. National Cancer Institute. Specifically, in this context, local drifts represent the log‐linear trends by period and birth cohort for each age group and indicate the annual percentage change of the expected age‐specific rates over time, whereas net drifts represent the overall log‐linear trends by period and birth cohort and indicate the overall APC of the expected age‐standardized rates over time. The Wald chi-squared test was performed to determine the significance of trends in APC. [ 21 ] The longitudinal age curve depicts the age‐specific and cohort-specific rates adjusted for period deviations, which is generally considered superior to a cross‐sectional age curve in assessing age effects. The relative risk (RR) of the cohort (or period) represents the cohort RR (or period RR) adjusted for age and non-linear period (or cohort) effects compared with the reference cohort (or period). When the RR value was >1, it suggested that the factor increases the risk of pancreatitis incidence or mortality; whereas, when the RR value was <1, it suggested that the factor decreases the risk of pancreatitis incidence or mortality. In a typical age–period–cohort analysis, age intervals must be equal to period intervals. Therefore, seven distinct 5-year age groups (65–69, 70–74, 75–79, 80–84, 85–89, 90–94, and ≥95 years) were adopted for further analysis. Correspondingly, the time period from 1992 to 2021 was divided into six 5-year periods (1992–1996, 1997–2001, 2002–2006, 2007–2011, 2012–2016, and 2017–2021). Therefore, 12 consecutive 5-year birth cohort groups were also used (1947–1951, 1952–1956, 1957–1961, 1962–1966, 1967–1971, 1972–1976, 1977–1981, 1982–1986, 1987–1991, 1992–1996, 1997–2001, and 2002–2006). To estimate the burden of pancreatitis among older people over the next 23 years, the case number, ASIR, and ASDR of pancreatitis among people aged ≥65 years were predicted using the Nordpred package in the R software (R Foundation for Statistical Computing; Vienna, Austria). This package considers shifting demographics and rates, which have been shown to be effective in predicting future changes in disease incidence and mortality. [ 22 ] First, we downloaded the observational and projected demographic data and predicted demographic data of pancreatitis in the older from 1992 to 2021 from the GBD 2021 database. Next, we used the R package Nordpred to forecast the future trend burden of pancreatitis among the older.We selected 2044 as the prediction endpoint, consistent with international practice for disease-burden projections using the Nordpred model. Several recent high-impact studies using this framework have likewise defined 2044 as the endpoint. [ [23] , [24] ] To quantify the drivers of changes in the number of incident cases and deaths of pancreatitis among older people, decomposition analysis was performed based on the method proposed by Das Gupta. [ 25 ] This method decomposes changes in the number of cases into population growth, aging, and epidemiological change. A series of decomposition analyses was performed with 1992 as the reference year, which was compared against all subsequent years up to 2021. The statistical procedures were conducted using the R program (version 4.3.2; R Core Team). P < 0.05 was considered statistically significant.

Globally, the estimated global ASIR and ASDR of pancreatitis among people aged ≥65 years were 85.20 (95% CI: 59.10 to 118.00) and 7.97 (95% CI: 6.84 to 9.41) in 2021, respectively ( Table 1 , Table 2 , Supplementary Tables S1 and S2). From 1992 to 2021, the estimated global ASIR of pancreatitis among people aged ≥65 years displayed a significant decreasing trend (AAPC= −0.57%; 95% CI: −0.59 to −0.55; P <0.001), with the most substantial changes occurring during 1996–2000 (APC= −2.09%; 95% CI: −2.19 to –2.00; P <0.001) (Supplementary Table S3). Similarly, the estimated global ASDR of pancreatitis among people aged ≥65 years also indicated a significant decline (AAPC= −0.45%; 95% CI,: −0.66 to −0.25; P <0.001) with the most substantial changes occurring during 2008–2021 (APC= −1.13%; 95% CI: −1.21 to −1.04; P <0.001) (Supplementary Table S3) overall. The APC model estimated net drifts of both the incidence and mortality of pancreatitis among people aged ≥65 years to be −0.58% (95% CI: −0.63 to −0.54) and −0.29% (95% CI: −0.36 to −0.22) (Supplementary Table S4). In addition, the incidence of pancreatitis demonstrated decreasing trends across all age groups (Supplementary Figure S1A). The mortality of pancreatitis showed decreasing trends from the 65–69-year group to the 85–89-year group, and an increased change was primarily found among individuals >90 years old (Supplementary Figure S1B). Table 1 The incident cases and ASIR of pancreatitis among people aged ≥65 years in 1992 and 2021 at global and regional levels. Table 1: dummy alt text Location Incident number in 1992 (95% CI) Incident number in 2021 (95% CI) ASIR in 1992 * (95% CI) ASIR in 2021 * (95% CI) Global 335,489.18 (220,407.59– 482,176.63) 289,886.74 (199,199.62– 403,176.36) 100.21 (65.85– 144.14) 85.20 (59.10–118.00) SDI quintiles High SDI 123,197.69 (83,804.65– 172,277.31) 213,432.95 (162,548.38– 275,776.99) 114.11 (77.52– 159.72) 103.00 (78.48–132.96) High-middle SDI 105,754.54 (70,596.06– 150,068.87) 181,859.15 (125,208.99– 253,514.38) 122.24 (81.66– 173.68) 100.10 (68.97–139.58) Middle SDI 68,030.08 (41,414.24– 102,526.28) 155,838.88 (99,573.04– 227,946.96) 84.52 (51.50– 127.40) 66.37 (40.67–99.97) Low-middle SDI 28,641.29 (17,416.86– 43,340.30) 74,526.63 (45,683.45– 112,242.08) 62.38 (37.94– 94.38) 59.36 (36.10–89.74) Low SDI 9435.08 (5726.82– 14,349.57) 21,403.63 (13,023.57– 32,359.56) 57.17 (34.67– 86.88) 59.36 (36.10–89.74) GBD regions Andean Latin America 1941.76 (1269.22– 2793.60) 5436.42 (3834.90– 7480.43) 114.27 (74.68– 164.56) 108.92 (76.86–149.87) Australasia 2549.50 (1603.57– 3771.67) 5336.69 (3371.35– 7900.03) 108.67 (68.21– 160.97) 101.46 (64.14– 149.91) Caribbean 1772.00 (1097.82– 2631.06) 3578.71 (2215.72– 5325.92) 75.85 (46.91– 112.75) 74.94 (46.43–111.42) Central Asia 3644.64 (2265.40– 5380.57) 5909.04 (3818.62– 8570.20) 98.70 (61.36– 145.92) 98.98(63.98–143.79) Central Europe 17,856.05 (12142.04– 25058.00) 23,981.11 (18,546.04– 30,592.54) 133.22 (90.47– 187.61) 107.56 (83.15– 137.25) Central Latin America 5911.16 (3823.63– 8607.58) 19,137.15 (12,601.16– 27,392.77) 87.55 (56.52– 127.72) 90.86 (59.88– 130.05) Central Sub-Saharan Africa 776.46 (464.57–1189.21) 1673.81 (1001.14– 2551.27) 50.37 (30.12– 77.08) 50.25 (30.05– 76.60) East Asia 73,594.31 (44,054.49– 112,229.35) 145,667.82 (92,691.20– 213,195.99) 107.14 (64.04– 163.62) 74.52 (47.37– 109.16) Eastern Europe 42,687.78 (27,075.92– 62,579.89) 61,422.00 (39,001.41– 90,017.19) 171.08 (108.39– 251.24) 183.39 (116.37– 268.93) Eastern Sub-Saharan Africa 2813.15 (1695.64– 4275.29) 6005.28 (3609.43– 9133.64) 51.90 (31.26– 78.84) 52.31 (31.47– 79.52) High-income Asia Pacific 12,112.85 (7409.27– 18142.55) 23,553.09 (15207.52– 33662.53) 64.86 (39.60, 97.34) 49.46 (31.92, 70.43) High-income North America 61,926.80 (41974.46, 87019.19) 105,210.76 (83,384.35– 131447.21) 173.89 (117.82– 244.43) 163.56 (129.73– 204.28) North Africa and Middle East 10,970.67 (6872.39, 16,312.93) 28,221.93 (18,752.52, 40,488.32) 87.52 (55.01– 129.88) 86.79 (57.81– 124.26) Oceania 125.64 (75.96– 190.07) 287.80 (174.11– 434.50) 63.39 (38.29– 95.97) 61.72 (37.36– 93.15) South Asia 24,618.35 (14,880.38– 37371.56) 77,604.08 (47,186.63– 117,282.13) 58.05 (35.10– 88.07) 65.68 (39.91– 99.31) Southeast Asia 10,615.01 (6471.43– 15,935.75) 26,149.87 (16,315.50– 38,667.56) 54.11 (32.97– 81.31) 51.57 (32.21– 76.29) Southern Latin America 3752.88 (2520.22– 5343.83) 7082.77 (4706.61– 10,087.02) 87.24 (58.49– 124.34) 87.17 (57.92– 124.12) Southern Sub-Saharan Africa 1272.49 (771.40–1931.88) 2455.54 (1476.99– 3732.86) 57.20 (34.64– 86.77) 56.04 (33.72– 85.20) Tropical Latin America 3600.49 (2491.00– 4973.93) 10,479.82 (7195.81– 14,527.32) 48.62 (33.65– 67.35) 47.53 (32.66– 65.87) Western Europe 48,872.49 (36,223.49– 64,356.35) 80,425.97 (61,682.66– 103,380.61) 84.54 (62.59– 111.40) 85.33 (65.31– 109.78) Western Sub-Saharan Africa 4074.71 (2458.38– 6198.65) 8065.65 (4853.74– 12,253.89) 59.96 (36.13– 91.15) 60.51 (36.41– 91.91) ASIR: Age-standardized incidence rate; CI: Confidence interval; GBD: Global Burden of Disease; SDI: Sociodemographic Index. ⁎ ASIR were presented as an estimate per 100,000 people. Table 2 The deaths and ASDR of pancreatitis among people aged ≥65 years in 1992 and 2021 at global and regional levels. Table 2: dummy alt text Location Deaths in 1992 (95% CI) Deaths in 2021 (95% CI) ASDR in 1992 * (95% CI) ASDR in 2021 * (95% CI) Global 28,491.52 (24,456.22– 33,019.77) 57,866.95 (49,521.28– 69,216.87) 9.01 (7.70– 10.43) 7.97 (6.84–9.41) SDI quintiles High SDI 8357.48 (7592.75– 8833.09) 13,172.22 (11,226.84– 143,33.12) 7.84 (7.09–8.30) 5.93 (5.11– 6.42) High-middle SDI 8086.66 (7319.72– 8860.12) 16,632.86 (14,657.02– 18,981.95) 10.14 (9.08– 11.14) 9.46 (8.30–10.80) Middle SDI 1476.55 (1003.76– 2140.07) 14,816.74 (12,242.71– 18,731.90) 8.22 (6.33–10.45) 7.10 (5.82–8.96) Low-middle SDI 4638.08 (3180.34– 6305.31) 10,272.92 (7914.26– 13,873.77) 10.51 (7.15– 14.39) 9.61 (7.39–12.94) Low SDI 1476.55 (1003.76– 2140.07) 2900.59 (2237.29– 4045.48) 9.51 (6.31–13.91) 8.63 (6.62–12.08) GBD regions Andean Latin America 285.91 (210.98– 388.46) 720.18 (526.69–969.79) 17.31 (12.79– 23.51) 14.60 (10.68– 19.66) Australasia 153.01 (131.79–173.91) 317.90 (254.74–372.65) 6.82 (5.84–7.77) 5.67 (4.56–6.65) Caribbean 172.25 (149.06–196.48) 308.51 (256.06–364.18) 7.64 (6.60–8.73) 6.41 (5.33–7.56) Central Asia 414.54 (349.36–489.06) 572.80 (483.37–677.79) 11.58 (9.73–13.73) 10.24 (8.65– 12.10) Central Europe 1855.07 (1723.35– 1980.01) 3074.64 (2734.81– 3376.59) 14.52 (13.41– 15.53) 13.85 (12.31– 15.21) Central Latin America 659.28 (614.17–698.58) 2128.79 (1847.50– 2377.31) 9.97 (9.24–10.59) 10.30 (8.94– 11.49) Central Sub-Saharan Africa 79.01 (43.09–145.10) 160.24 (91.30–278.67) 5.56 (2.95–10.23) 5.04 (2.85–8.68) East Asia 3609.55 (2715.44– 4911.04) 7908.69 (5925.65– 10,783.58) 6.29 (4.67–8.61) 4.49 (3.36–6.10) Eastern Europe 2257.90 (2106.33– 2400.70) 6133.49 (5527.88– 6666.18) 9.24 (8.59–9.83) 18.52 (16.68– 20.13) Eastern Sub-Saharan Africa 302.46 (175.66–529.58) 599.81 (361.41–957.19) 5.86 (3.29–10.38) 5.52 (3.29–8.85) High-income Asia Pacific 1093.13 (953.50–1189.54) 1872.43 (1457.62– 2172.09) 6.36 (5.47–6.94) 3.19 (2.56–3.68) High-income North America 2195.94 (1960.15– 2343.16) 3675.41 (3140.03– 3979.74) 6.16 (5.49–6.58) 5.60 (4.80–6.05) North Africa and Middle East 747.54 (486.33–1146.32) 2038.96 (1500.87– 2794.00) 7.09 (4.52–10.91) 7.27 (5.32–9.96) Oceania 7.07 (3.14–12.00) 12.90 (6.81–21.51) 3.58 (1.61–6.00) 2.71 (1.45–4.49) South Asia 4480.06 (2890.37– 6307.54) 10,212.46 (7548.89, 13,929.98) 10.96 (6.98– 15.59) 9.07 (6.67–12.37) Southeast Asia 2096.25 (1403.78– 2985.67) 4466.78 (3350.11– 6942.93) 11.80 (7.79–16.91) 9.77 (7.30–15.15) Southern Latin America 677.30 (587.41–769.71) 968.98 (830.59– 1109.24) 16.13 (13.95– 18.35) 11.84 (10.15– 13.55) Southern Sub-Saharan Africa 92.40 (53.29–135.68) 194.39 (132.84–242.01) 4.33 (2.49–6.31) 4.67 (3.17–5.81) Tropical Latin America 748.98 (683.26–808.79) 2726.29 (2364.04– 2975.72) 10.53 (9.50–11.41) 12.58 (10.88– 13.74) Western Europe 5736.55 (5184.82– 6120.90) 8022.70 (6710.72– 8823.40) 9.98 (8.99–10.66) 7.68 (6.53–8.41) Western Sub-Saharan Africa 827.32 (570.35–1181.30) 1750.60 (1175.09– 2408.30) 12.93 (8.92–18.65) 14.12 (9.50–19.64) ASDR: Age-standardized death rate; CI: Confidence interval; GBD: Global Burden of Disease; SDI: Sociodemographic Index. ⁎ ASDR were presented as an estimate per 100,000 people. The incident cases and ASIR of pancreatitis among people aged ≥65 years in 1992 and 2021 at global and regional levels. ASIR: Age-standardized incidence rate; CI: Confidence interval; GBD: Global Burden of Disease; SDI: Sociodemographic Index. ASIR were presented as an estimate per 100,000 people. The deaths and ASDR of pancreatitis among people aged ≥65 years in 1992 and 2021 at global and regional levels. ASDR: Age-standardized death rate; CI: Confidence interval; GBD: Global Burden of Disease; SDI: Sociodemographic Index. ASDR were presented as an estimate per 100,000 people. Across the five SDI regions, the ASIR of pancreatitis decreased from the high SDI quintile (103.00; 95% CI: 78.48 to 132.96) to the low SDI quintile (59.36; 95% CI: 36.10 to 89.74), whereas the ASDR was highest in the low-middle SDI quintile (9.61; 95% CI: 7.39 to 12.94) and lowest in the high SDI quintile (5.93; 95% CI,: 5.11 to 6.42) in 2021 ( Table 1 , Table 2 ). From 1992 to 2021, the increasing trend in ASIR was only observed in low-middle SDI and low SDI regions, while decreases were noted in high SDI, high-middle SDI, and middle SDI regions (Supplementary Table S3). There was also a decreasing trend in ASDR in the high SDI and middle SDI regions (Supplementary Table S3). Similar patterns could be seen in the net drift results estimated by the APC model (Supplementary Table S4). In addition, the trends in pancreatitis incidence generally developed decreased patterns among different age groups over time in all SDI regions except low-middle SDI regions and low SDI regions, where they instead experienced positive local drifts and increasing trends (Supplementary Figure S1A). The trends in pancreatitis mortality have also generally developed decreased trends in the younger groups, but increased trends were noted in the older groups in all SDI regions (Supplementary Figure S1B). By geographical category, Eastern Europe yielded the highest estimated global ASIR and ASDR of pancreatitis among people aged ≥65 years, while the lowest values were computed for Tropical Latin America and Oceania in 2021, respectively ( Table 1 , Table 2 ). From 1992 to 2021, the most significant decreases in ASIR and ASDR occurred in East Asia and the high-income Asia Pacific, respectively, whereas the greatest increase occurred in Eastern Europe (Supplementary Table S3). In addition, a positive correlation was found between the ASIR of older pancreatitis and SDI, whereas ASDR did not show a significant correlation with SDI level ( Figure 1 A, and Supplementary Figure S2A). Figure 1 The ASIR of pancreatitis among people aged ≥65 years for (A) 21 GBD regions from 1992 to 2021 and (B) 204 countries and territories in 2021 by SDI. ASIR: Age-standardized incidence rate; GBD: Global Burden of Disease; SDI: Sociodemographic Index. Figure 1: dummy alt text The ASIR of pancreatitis among people aged ≥65 years for (A) 21 GBD regions from 1992 to 2021 and (B) 204 countries and territories in 2021 by SDI. ASIR: Age-standardized incidence rate; GBD: Global Burden of Disease; SDI: Sociodemographic Index. At the national level, the estimated ASIR and ASDR showed significant variations across 204 countries and territories, with the highest ASIR and ASDR values recorded for Denmark and Bhutan and the lowest recorded for Nicaragua and Gabon in 2021 (Supplementary Tables S1 and S2). From 1992 to 2021, the country with the greatest increase in ASIR among older people with pancreatitis was Singapore (2.33%), while Poland recorded the lowest ASIR overall (−1.87%) (Supplementary Table S3). Over the same period, Guam showed the most substantial decrease in ASDR among older people with pancreatitis (−6.22%), followed by Cyprus (−4.16%). Meanwhile, the country with the greatest increase in ASDR among older people with pancreatitis was Georgia (9.95%). In addition, the patterns of changes in ASIR and ASDR of pancreatitis with increased SDI at the national level were similar to those at the 21 regional levels ( Figure 1 B and Supplementary Figure S2B). The age, period, and cohort effects on the incidence and mortality of pancreatitis among older people derived from the age–period–cohort analysis are demonstrated in Figure 2 , Figure 3 . For the incidence risk of pancreatitis among older people, similar age-related patterns were observed across all SDI quintiles with the risk, increasing trend with age ( Figure 2 A). High and high-middle SDI regions displayed an overall higher incidence rate across all age groups as compared to other SDI regions. The period effects revealed a decrease in the risk of incidence since 1992 globally ( Figure 2 B). In middle, high-middle, and high SDI regions, period effects have been deescalating over time. Middle SDI regions showed a considerably decreased risk from 1992-1996 to 2002-2006, after which the risk gradually increased. Also, the incidence risk of pancreatitis among older people in low-middle and low SDI regions remained essentially increased over the previous three decades, indicating that the occurrence of pancreatitis has not been effectively controlled over time. Finally, the cohort effects showed a significant decrease from earlier to later birth cohorts globally ( Figure 2 C). Similar patterns were observed in the high SDI, high-middle SDI, and middle SDI regions. The cohort effect showed a slight increase in incidence risk from earlier birth cohorts to more recent birth cohorts in low-middle and low SDI regions. Figure 2 The age–period–cohort effects on the incidence of pancreatitis among people aged ≥65 years in global and five SDI regions. A: Longitudinal age curve. B: Period rate ratio. C: Cohort rate ratio. SDI: Sociodemographic Index. Figure 2: dummy alt text Figure 3 The age–period–cohort effects on the mortality of pancreatitis among people aged ≥65 years in global and five SDI regions. A: Longitudinal age curve. B: Period rate ratio. C: Cohort rate ratio. SDI: Sociodemographic Index. Figure 3: dummy alt text The age–period–cohort effects on the incidence of pancreatitis among people aged ≥65 years in global and five SDI regions. A: Longitudinal age curve. B: Period rate ratio. C: Cohort rate ratio. SDI: Sociodemographic Index. The age–period–cohort effects on the mortality of pancreatitis among people aged ≥65 years in global and five SDI regions. A: Longitudinal age curve. B: Period rate ratio. C: Cohort rate ratio. SDI: Sociodemographic Index. As for the mortality risk of pancreatitis among older people, it increased with age like incidence risk and reached its highest point in older people ≥95 years old ( Figure 3 A). The period effects presented a declining risk of mortality globally and across different SDI regions except low-middle SDI and low SDI regions ( Figure 3 B). Regarding birth cohort effects, there was a declining risk of mortality in successive birth cohorts globally ( Figure 3 C). High SDI regions had favorable mortality improvements in successive birth cohorts, whereas mortality in other SDI regions remained nearly constant over the past two decades, indicating little improvement. The incidence and mortality numbers of pancreatitis cases among older people are projected to continue increasing among both men and women until 2044 ( Figure 4 ). In 2044, the overall number of new pancreatitis cases among older people should increase to 1228,005, whereas the number of pancreatitis deaths among older people should increase to 107,884. However, the ASIR and ASDR in both men and women are expected to continue declining throughout the period to 2044; in 2044, the ASIR should decrease to 83.16, whereas the ASDR should decrease to 7.02. Figure 4 The global trends in (A and B) incident number and ASIR and (C and D) deaths and ASDR, respectively, of pancreatitis among people aged ≥65 years from 1992 to 2044. *The observed rates are plotted with solid lines, while predicted rates are plotted with dashed lines. ASDR: Age-standardized death rate; ASIR: Age-standardized incidence rate. Figure 4: dummy alt text The global trends in (A and B) incident number and ASIR and (C and D) deaths and ASDR, respectively, of pancreatitis among people aged ≥65 years from 1992 to 2044. *The observed rates are plotted with solid lines, while predicted rates are plotted with dashed lines. ASDR: Age-standardized death rate; ASIR: Age-standardized incidence rate. Our decomposition analysis provided insights into the relative contributions of aging, population, and demographically adjusted changes in epidemiology to the numbers of incident and death cases of pancreatitis among older people between 1992 and 2021 (Supplementary Figure S3). In terms of global incident cases, 115.21% of the increase in pancreatitis among older people over time was attributed to population growth, followed by population aging (2.25%), while epidemiological changes offset the burden by −24.41% (Supplementary Table S5). Like the number of global incident cases, a similar attribution also existed among the number of global death cases (Supplementary Table S6). Although high SDI, high-middle SDI, and middle SDI regions exhibited declining demographically adjusted epidemiological changes, all five SDI region types experienced an increase in the number of pancreatitis incident cases between 1992 and 2021, primarily due to population growth. Despite declining demographically adjusted epidemiological changes across all five SDI regions, all region types also experienced an increase in deaths between 1992 and 2021. Two regions with significant declining demographically adjusted epidemiological changes, East Asia and the high-income Asia Pacific, experienced an increase in the numbers of incident and death cases of pancreatitis among older adults people between 1992 and 2021, with population growth being the main contributor.

In this study, we used data from GBD 2021 to calculate the ASIR and ASDR of pancreatitis among people aged ≥65 years from 1992 to 2021 and examined their changing trends at global, regional, and national levels. Given the complex interplay among age, period, and cohort effects, we explored the relative impact of these variables on the incidence and mortality trends of pancreatitis. In addition, we predicted the global numbers and rates of incidence and mortality up to 2044. All of these data are important for the rational allocation of health resources. In 2021, there were notable variations in both the ASIR and ASDR of pancreatitis in the older adults at global, regional, and national levels. This suggests substantial heterogeneity in the disease’s burden across different areas, potentially attributable to various factors such as genetic variations and environmental exposures. [ [26] , [27] , [28] ] What is particularly noteworthy is the interesting clustering of pancreatitis in relatively developed areas, where the ASIR of pancreatitis in the older adults shows a positive correlation with the SDI level. This is consistent with findings of a previous study indicating that countries with higher levels of SDI may face a greater burden of pancreatitis. [ 29 ] Several potential reasons might explain this phenomenon. First, alcohol is considered the primary cause of pancreatitis in most developed countries, and an increase in alcohol consumption among the older adults in these regions may correspondingly elevate the risk of the disease. [ 27 , 30 ] Second, environmental factors play a crucial role in the development of pancreatic cancer; most developed countries have undergone industrialization, urbanization, and modernization, inevitably leading to the production of harmful substances that contribute to pancreatitis. [ 31 ] Finally, due to the relatively robust healthcare systems in high SDI areas, older patients with pancreatitis are more likely to be diagnosed and treated. In addition, considering the limited data collection in regions with underdeveloped medical systems, the overall burden of older pancreatitis may be much heavier than observed. From 1992 to 2021, the global ASIR and ASDR of older pancreatitis showed a significant downward trend, indicating that overall substantial progress has been made in the management of pancreatitis over the past few decades. At the regional level, the estimated ASIR and ASDR of pancreatitis in older people show varying trends across different areas. Notably, unlike the declining trends in ASIR and ASDR from 1992 to 2021 in high SDI regions, regions with relatively low SDI exhibited increasing trends, suggesting ongoing issues in the management of older pancreatitis in lower SDI areas. Factors such as population growth and migration, changes in alcohol consumption and smoking patterns, rising obesity rates, an enhanced understanding of the metabolic causes of pancreatitis, and improvements in imaging techniques and quality may collectively explain the differences in such trends. [ 31 ] Moreover, the variations in the estimated ASIR and ASDR among 204 countries and regions are substantial, indicating significant disparities in the prevention and treatment of older pancreatitis. Identifying the unique trend changes in each country or region is crucial for governments to improve their healthcare systems to meet the diverse medical needs associated with older pancreatitis. The age effect explains how incidence and mortality rates of pancreatitis in the older adults change with age, reflecting evolutions related to growth and aging during the life course. Our study indicated that the risk of both incidence and mortality gradually increases with increasing age. Previous studies have reported similar patterns in the risk of incidence and mortality rates for pancreatitis. [ [32] , [33] , [34] ] For example, Spanier et al. [ 33 ] showed that the incidence and mortality rates of acute pancreatitis (AP) and chronic pancreatitis (CP) significantly increase with age. A prospective cohort study by Moran et al. [ 35 ] indicated that being >85 years of age is associated with a higher rate of mortality from acute pancreatitis. The high risk of incidence for pancreatitis in the older adults could be attributable to increased exposure to risk factors such as biliary and metabolic disorders, while the high risk of mortality may relate to a progressive decline in the physiological function of major organs with aging. [ 7 , 36 , 37 ] The period effect showed that both incidence and mortality rates have significantly decreased globally, where advancements in healthcare may play an important role. Over the past few decades, research related to pancreatitis has seen significant improvements in both quantity and quality. [ 38 , 39 ] Numerous high-quality basic and clinical research studies continue to advance the management of pancreatitis. Notably, the risks of incidence and mortality for pancreatitis among older people in low SDI regions have not been controlled as time progresses. The cohort effect demonstrated that different birth cohorts have an impact on the incidence and mortality rates of older pancreatitis, which indicates changes in exposure to environmental risk factors or lifestyle changes within the specific birth cohort. The cohort effect on the incidence and mortality of pancreatitis in the older adults exhibited a decreasing trend from earlier birth cohorts to more recent birth cohorts. A potential reason is that later-born cohorts generally possess higher educational levels and stronger disease awareness. At the same time, earlier-born cohorts might have undergone wars, which not only worsened living and hygiene conditions but also directly threatened life and health. Furthermore, advancements in medical technology have contributed to reductions in the risk of incidence and death from older pancreatitis. It is also noteworthy that, in lower-SDI regions, the RR of older pancreatitis incidence is increased in more recent birth cohorts. In summary, the overall decline in incidence and mortality rates over time is encouraging for older pancreatitis patients and their families globally. For policymakers, there is an urgent need to ready healthcare resources for the increasing risk of older individuals suffering from pancreatitis in the relatively low SDI regions. In clinical practice, it is necessary to strengthen the training of medical staff to enhance their focus on older pancreatitis. Moreover, older patients are encouraged to place great importance on the treatment of pancreatitis. We also used decomposition analysis to elucidate the crucial roles of demographic and epidemiological changes in the occurrence and progression of older pancreatitis. Over the past 30 years, there have been significant advancements in the diagnosis and treatment of older pancreatitis due to improvements in global healthcare. It should also be noted that the positive effects of epidemiological changes are offset by population growth and aging. Our results indicated that the global ASIR and ASDR for older pancreatitis are expected to decrease from 2022 to 2044. Conversely, however, the numbers of incident cases and deaths are expected to increase, which might also be related to population growth and aging. On the one hand, the United Nations expects a continuous increase in the global population, reaching 8.5 billion by 2030 and 9.7 billion by 2050. [ 40 ] On the other hand, the rapidly increasing aging population worldwide may also contribute to a higher burden of older pancreatitis. Thus, governments should take into account the potential health impacts of aging populations and population growth when devising or modifying health-prevention strategies. This study has the following strengths. First, our investigation covered a wide geographic area and a large time span based on a large amount of data. Second, the estimation of age-standardized morbidity and mortality rates of pancreatitis in the older adults overcomes the heterogeneity of the age structure and thus facilitates valid comparisons between different regions. Finally, age–period–cohort modeling was used to distinguish the independent effects of age, period, and cohort effects on the risk of incidence and mortality of pancreatitis in the older adults. However, there are also several limitations to consider. First, imperfections in the healthcare systems of less-developed countries may lead to an underestimation or overestimation of disease burden. Second, we depended heavily on modeling procedures for estimations, and the models and parameter settings we chose may have affected our results. Third, it was not possible to explore the characterization of epidemiological trends in pancreatitis in the older adults at the subnational level due to a lack of detailed data. Fourth, some of the symptoms of pancreatitis are mild and self-limiting and thus may go unrecognized in patients who do not seek medical care, which may allow the burden of pancreatitis to be underestimated. Fifth, similar to other APC analyses, ours is inevitably subject to ecological fallacy, as interpretations of population-level results do not necessarily apply to individuals. Finally, data were extrapolated from existing epidemiologic data, and thus, interpreting our results in the real world requires caution.

In summary, our study revealed that, from 1992 to 2021, the global trends in ASIR and ASDR for older pancreatitis were highly heterogeneous, with developed countries bearing a higher burden of ASIR and undeveloped countries facing poor disease management over the past three decades. In addition, we forecast an increase in the number of incident and death cases of older pancreatitis by 2044. These findings further highlight the significant challenges that exist in controlling older pancreatitis, providing direction for policymakers to adopt strategies based on regional characteristics and to improve equity in the management of older pancreatitis.

Population aging is a defining global trend of our time. Data suggest that the global population aged ≥65 years has increased from 0.36 billion to 0.81 billion over the past 30 years. [ 1 ] Aging generally leads to reduced health quality and affects the structure and function of various organs, including the pancreas. [ 2 ] Pancreatitis is an inflammatory disease of the pancreas that imposes significant burdens on public health and the economy. [ 3 ] Among the older individuals, pancreatitis is a major cause of acute abdominal pain, marked by sudden changes and varied symptoms such as abdominal bloating, pain, nausea, jaundice, and shock. [ [4] , [5] , [6] ] Moreover, pancreatitis in older patients is frequently complicated by hypertension, coronary heart disease, and diabetes, which may result in multiorgan dysfunction and higher mortality rates. [ 5 , 7 ] Undoubtedly, exploring the global trends of pancreatitis in the older adults is vital for crafting targeted intervention strategies. However, most previous studies have focused solely on national or regional levels. [ 5 , [7] , [8] , [9] , [10] ] In addition, results from descriptive analyses might be influenced by interactions among age, period, and cohort effects. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is a reliable tool for systematically assessing disease burden whose 2021 version assessed the burden of 371 diseases, injuries, and impairments and 88 risk factors across 204 countries and territories. [ 11 ] So far, data from GBD 2021 have been instrumental in various analytical frameworks, including disease burden descriptions, trend analyses, future projections, and health inequality monitoring. [ [11] , [12] , [13] ] In this study, we used data from GBD 2021 to explore the epidemiological characteristics of pancreatitis in adults aged ≥65 years from 1992 to 2021; analyze the impact of age, period, and birth cohorts on disease burden; and predicted the incidence and mortality of pancreatitis. With this work, we seek to provide a solid foundation for developing scientific and effective prevention and intervention strategies.