research articles on ulcer

Click through the PLOS taxonomy to find articles in your field.

For more information about PLOS Subject Areas, click here .

Loading metrics

Open Access

Peer-reviewed

Research Article

Quality of care of peptic ulcer disease worldwide: A systematic analysis for the global burden of disease study 1990–2019

Roles Conceptualization, Investigation, Writing – original draft

¶ ‡ MAK and NA share co-first author on this work.

Affiliation Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Roles Conceptualization, Methodology, Visualization, Writing – review & editing

Roles Conceptualization, Investigation, Writing – review & editing

Affiliations Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran, Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Roles Conceptualization, Data curation, Investigation, Writing – review & editing

Affiliations Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran, Department of Biostatistics, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran

Roles Investigation

Affiliation Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Roles Formal analysis, Investigation, Writing – review & editing

Affiliations Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran, The Netherlands Cancer Institute(NKI), Amsterdam, Netherlands

Roles Investigation, Writing – review & editing

Affiliation Student Research Committee, Kurdistan University of Medical Sciences, Sanandaj, Iran

Affiliations Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran, Elderly Health Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

Roles Conceptualization, Resources, Supervision, Writing – review & editing

Affiliation Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

•  [ ... ],

Roles Conceptualization, Methodology, Resources, Supervision, Writing – review & editing

* E-mail: [email protected]

• [ view all ]
• [ view less ]
• Mohsen Abbasi-Kangevari, 
• Naser Ahmadi, 
• Nima Fattahi, 
• Negar Rezaei, 
• Mohammad-Reza Malekpour, 
• Seyyed-Hadi Ghamari, 
• Sahar Saeedi Moghaddam, 
• Sina Azadnajafabad, 
• Zahra Esfahani, 

• Published: August 1, 2022
• https://doi.org/10.1371/journal.pone.0271284
• Peer Review
• Reader Comments

Peptic ulcer disease (PUD) affects four million people worldwide annually and has an estimated lifetime prevalence of 5−10% in the general population. Worldwide, there are significant heterogeneities in coping approaches of healthcare systems with PUD in prevention, diagnosis, treatment, and follow-up. Quantifying and benchmarking health systems’ performance is crucial yet challenging to provide a clearer picture of the potential global inequities in the quality of care.

The objective of this study was to compare the health-system quality-of-care and inequities for PUD among age groups and sexes worldwide.

Data were derived from the Global Burden of Disease Study 1990–2019. Principal-Component-Analysis was used to combine age-standardized mortality-to-incidence-ratio, disability-adjusted-life-years-to-prevalence-ratio, prevalence-to-incidence-ratio, and years-of-life-lost-to-years-lived-with-disability-into a single proxy named Quality-of-Care-Index (QCI). QCI was used to compare the quality of care among countries. QCI’s validity was investigated via correlation with the cause-specific Healthcare-Access-and-Quality-index, which was acceptable. Inequities were presented among age groups and sexes. Gender Disparity Ratio was obtained by dividing the score of women by that of men.

Global QCI was 72.6 in 1990, which increased by 14.6% to 83.2 in 2019. High-income-Asia-pacific had the highest QCI, while Central Latin America had the lowest. QCI of high-SDI countries was 82.9 in 1990, which increased to 92.9 in 2019. The QCI of low-SDI countries was 65.0 in 1990, which increased to 76.9 in 2019. There was heterogeneity among the QCI-level of countries with the same SDI level. QCI typically decreased as people aged; however, this gap was more significant among low-SDI countries. The global Gender Disparity Ratio was close to one and ranged from 0.97 to 1.03 in 100 of 204 countries.

QCI of PUD improved dramatically during 1990–2019 worldwide. There are still significant heterogeneities among countries on different and similar SDI levels.

Citation: Abbasi-Kangevari M, Ahmadi N, Fattahi N, Rezaei N, Malekpour M-R, Ghamari S-H, et al. (2022) Quality of care of peptic ulcer disease worldwide: A systematic analysis for the global burden of disease study 1990–2019. PLoS ONE 17(8): e0271284. https://doi.org/10.1371/journal.pone.0271284

Editor: Dinh-Toi Chu, International School, Vietnam National University, VIET NAM

Received: January 9, 2022; Accepted: June 27, 2022; Published: August 1, 2022

Copyright: © 2022 Abbasi-Kangevari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The study protocol and codes used in this study are available from ( https://dx.doi.org/10.17504/protocols.io.bprjmm4n ) [ 5 ]. The data used in this work are available from Global Burden of Disease Results Tool ( http://ghdx.healthdata.org/gbd-results-tool ) [ 6 ], made public by Institute for Health Metrics and Evaluation. The data of PUD were extracted from GBD 2019: GBD code: B.4.2.1, International Statistical Classification of Diseases and Related Health Problems 10th Revision, World Health Organization version 10 (ICD-10) code: K-25 to K28.9 [ 7 ]. Data sources used to provide estimates in GBD 2019 are presented in S1 Table . In terms of the development status, countries were categorized using the GBD Socio-Demographic Index (SDI) [ 8 ].

Funding: The author(s) received no specific funding for this work.

Competing interests: The authors have declared that no competing interests exist.

Introduction

Peptic ulcer disease (PUD) affects four million people worldwide annually [ 1 ] and has an estimated lifetime prevalence of 5−10% in the general population [ 2 ]. Although the global prevalence of PUD has dramatically decreased in the past decades [ 3 ], the incidence of its complications has remained constant [ 4 ].

Worldwide, there are significant heterogeneities in coping approaches of healthcare systems with PUD in terms of prevention, diagnosis, treatment, and follow-up [ 5 ]. Prevention is positively correlated with the development of infrastructures and the effectiveness of healthcare systems [ 6 ]. The choice of diagnostic test and treatment approaches mainly relies on accessibility and cost [ 7 ]. Therefore, quantifying and benchmarking health systems’ performance is crucial yet challenging to provide a clearer picture of the potential global inequities in the quality of care [ 8 ].

In this sense, the objective of this study was to compare the quality of medical care provided for PUD using the Quality of Care Index (QCI) among age groups and both sexes in various nations and regions based on the data of the Global Burden of Disease (GBD) Study 2019. To obtain QCI, four indices of PUD, including age-standardized mortality to incidence ratio, disability-adjusted life years (DALYs) to prevalence ratio, prevalence to incidence ratio, and years of life lost (YLLs) to years lived with disability (YLDs) ratio, were combined into a single index using Principal Component Analysis (PCA) [ 9 – 17 ].

Materials and methods

The study data were initially derived from the GBD study, conducted by Institute for Health Metrics and Evaluation (IHME), which abides by relevant guidelines and regulations. We carried out no experiments on any human or animal subjects. Thus, consent to participate does not apply to the present study. This study was approved by the institutional review board of Endocrinology and Metabolism Research Institute at Tehran University of Medical Sciences (IR.TUMS.EMRI.REC.1400.016).

Data source

The study data were derived from GBD 2019, conducted by IHME. GBD 2019 included 204 countries and territories from 1990 to 2019 and a systematic analysis of 286 causes of death, 369 diseases and injuries, and 87 risk factors in 204 countries and territories [ 18 , 19 ]. GBD classified countries and territories into 21 regions based on epidemiological homogeneity and geographical contiguity [ 20 ]. The regions were also grouped into seven super-regions based on the cause of death patterns [ 21 ]. The seven super-regions are High income; Latin America & Caribbean; Sub-Saharan Africa; North Africa & Middle East; Southeast Asia, East Asia & Oceania; South Asia; Central Europe, Eastern Europe & Central Asia.

The study protocol and codes used in this study are available from ( https://dx.doi.org/10.17504/protocols.io.bprjmm4n ) [ 22 ]. The data used in this work are available from Global Burden of Disease Results Tool ( http://ghdx.healthdata.org/gbd-results-tool ) [ 23 ], made public by Institute for Health Metrics and Evaluation. The data of PUD were extracted from GBD 2019: GBD code: B.4.2.1, International Statistical Classification of Diseases and Related Health Problems 10th Revision, World Health Organization version 10 (ICD-10) code: K-25 to K28.9 [ 24 ]. Data sources used to provide estimates in GBD 2019 are presented in S1 Table . In terms of the development status, countries were categorized using the GBD Socio-Demographic Index (SDI) [ 25 ].

Statistical analysis

Age standardization..

To account for the change in population structure, age-standardized incidence, mortality, YLLs, YLDs, and DALYs rates were computed by direct standardization to the global age structure and expressed as the number per 100,000 population [ 18 ]. Nevertheless, to investigate the inequities among age groups, all-ages measures were used to calculate QCI.

Quality of care index.

The mortality to incidence ratio of PUD indicates that with a stable PUD incidence in regions, higher mortality values could represent worse care provided to these patients.

DALY to prevalence ratio of PUD indicates that with a similar prevalence of PUD in regions, higher DALY could represent worse care quality.

The prevalence to incidence ratio of PUD indicates that in regions with similar PUD incidence, higher prevalence could represent better PUD management to avert mortality.

YLLs to YLDs ratio of PUD could reflect the quality of healthcare in a region, as poor health quality provided for PUD in a region would result in higher YLLs and fewer YLDs. In other words, patients would live less than the life expectancy of the region.

Principal components analysis.

PCA would allow us to reduce the number of variables in a large set of correlated variables to a smaller number of variables that collectively explain most of the variance in the original set [ 26 ]. The first component of PCA was made up of a linear combination of the four abovementioned ratios, including mortality to incidence, DALYs to prevalence, prevalence to incidence, and YLLs to YLDs, containing the most significant amount of information about these variables and is referred to as QCI in this study. QCI ranged from 0 to 100, with 100 indicating the best quality of care [ 9 – 11 , 17 , 22 ]. PCA would allow us to reduce the number of variables in a large set of correlated variables to a smaller number of variables that collectively explain most of the variance in the original set The interpretation of all the above measures could be used as a proxy for the quality of care provided for the disease. In this study, PCA was performed to convert the four indices into a single index. PCA is an approach to statistical analysis in which multiple datasets are combined as orthogonal components [ 26 ]. The first component of PCA was, made up of a linear combination of the four abovementioned ratios, including mortality to incidence, DALYs to prevalence, prevalence to incidence, and YLLs to YLDs, all variables, containings the greatest most significant amount of information about these variables and is referred to as QCI in this study. QCI ranged from 0 -to 100, with 100 indicating the best quality of care [ 9 – 11 , 17 , 22 ].

PCA was performed using R software version 3.5.2. For enhanced interpretation and comparison of countries, QCI was categorized as five levels in 2019 based on quintiles, where Level 1 (the first quintile) indicated the highest index and Level 5 (the fifth quintile) the lowest: Level 5 included QCI ≤69.14, Level 4 QCI>69.14 to 75.23, Level 3 QCI>75.23 to 81.33, Level 2 QCI>81.33 to 86.35, and Level 1 QCI>86.35.

Data validation.

Healthcare Access and Quality (HAQ) was another index for measuring personal healthcare access and quality across countries, developed by GBD in 2016 [ 27 ]. HAQ has been calculated for 32 causes, including PUD, that were considered amenable to health care comprise, representing a range of health service areas: vaccine-preventable diseases; infectious diseases and maternal and child health; non-communicable diseases, including cancers, cardiovascular diseases, and other non-communicable diseases such as diabetes; and gastrointestinal conditions from which surgery can avert death. Thus, the cause-specific HAQ reported for PUD could be used to validate QCI externally. The correlation between the QCI and all-causes/cause-specific HAQ index [ 28 , 29 ] was evaluated by applying a mixed-effect model of QCI as a dependent variable and inpatient and outpatient health care utilization, mortality of PUD, and its mortality attribute to smoking, which is its known risk factor reported by GBD [ 24 ], as independent variables while considering countries as random effects. The correlation between the HAQ Index and the predicted values was 0.72, indicating an acceptable association between the two indices [ 30 ] and validating QCI as an applicable measure of the quality of care among patients with PUD ( S2 Table ). Healthcare Access and Quality (HAQ) was another index for measuring personal health-care access and quality across countries, developed by GBD in 2016 [ 27 ]. HAQ has been calculated for 32 causes, including PUD, that were considered amenable to health care comprise, representing a range of health service areas: vaccine-preventable diseases; infectious diseases and maternal and child health; non-communicable diseases, including cancers, cardiovascular diseases, and other non-communicable diseases such as diabetes; and gastrointestinal conditions from which surgery can easily avert death. Thus, the cause-specific HAQ reported for PUD could be used to externally validate QCIvalidate QCI externally. The correlation between the QCI and all-causes/cause-specific HAQ index [ 28 , 29 ] was evaluated by applying a mixed-effect model of QCI as a dependent variable and inpatient and outpatient health care utilization, mortality of PUD, and its mortality attribute to smoking, which is its known risk factor reported by GBD [ 24 ], as independent variables while considering countries as random effects. The correlation between the HAQ Index and the predicted values was 0.72, indicating an acceptable association of between the two indices [ 30 ] and validating QCI as an applicable measure of the quality of care among patients with PUD ( S2 Table ).

Inequity pattern.

Geographical inequity . The age-standardized QCI among various locations were presented as a geographical hierarchy, including 204 countries and territories grouped into 21 regions and seven GBD super-regions [ 18 ].

Age inequity . Age inequity presented the status of quality of care across different age groups based on different SDI regions. All-ages data were used for determining the QCI among age groups.

Gender inequity . The age-standardized QCIs among both women and men were calculated separately and compared to determine the status of gender equity. Gender Disparity Ratio (GDR) was obtained by dividing the age-standardized QCI of women by that of men. The numbers closer to one indicate a better situation.

The statistical analyses were carried out in October 2020 using R statistical packages v3.4.3 ( http://www.r-project.org , RRID: SCR_001905). Data visualizations were performed using Python programming language (Python Language Reference, version 3.6. Available at www.python.org ) via Altair version 4.1, an open-source Python library. The maps were generated using free open-source map data of Natural Earth public domain (naturalearthdata.com) via Python programming language. The statistical codes are available elsewhere [ 22 ].

Prevalence, incidence, and mortality

Since 1990, the age-standardized prevalence of PUD has decreased 31% worldwide, from 143.4 per 100,000 to 99.4 in 2019. However, there was heterogeneity in the prevalence changes by geographical distribution. Among 21 GBD regions in 1990–2019, the age-standardized prevalence rate of PUD decreased by almost 70% in Andean Latin America, 58% in Latin America and Caribbean, and 37% in South Asia. PUD incidence has continuously decreased by 31% worldwide, from 63.8 in 1990 per 100,000 to 44.3 in 2019. The age-standardized incidence rate has decreased by almost 68% in Andean Latin America, 56% in Latin America and Caribbean, and 45% in Eastern Europe. The age-standardized mortality rate of PUD has 59% decreased, from 7.4 in 1990 to 3.0 in 2019. The highest age-standardized mortality of PUD was witnessed in low and low-middle SDI countries ( S3 and S4 Tables).

Quality of care index

Gbd regions..

Distinct geographic patterns emerged for QCI levels from 1990 to 2019. The global age-standardized QCI was 72.6 (Level 4) in 1990, which has increased by 14.6% to 83.2 (Level 2) in 2019. Among GBD regions, high-income Asia Pacific had the highest age-standardized QCI in 2019. Central Latin America had the lowest QCI in 1990, which increased by 154.9% from 20.1 (Level 5) to 51.2 (Level 5) in 2019. By 2019, nearly all countries and territories saw increases in their QCI, except for Armenia, Zimbabwe, Democratic People’s Republic of Korea, Brazil, Kazakhstan, Uzbekistan, Lesotho, Nepal, Ukraine, Pakistan, Lithuania, Tajikistan, and Paraguay. The top five countries with the highest QCI in 2019 included Singapore (98.5), Turkey (97.3), Japan (96.9), the Republic of Korea (96.9), and the United States of America (95.1). Honduras (13.2), Guatemala (27.0), Cambodia (40.2), El Salvador (41.1), and Nicaragua (43.5) had the lowest index. The gap between the highest and lowest QCI was narrower in 2019 (ΔQCI = 85.3) than in 1990 (ΔQCI = 89.3). QCI of countries in categories in 1990 and 2019 are presented in Fig 1 and S5 Table .

• PPT PowerPoint slide
• PNG larger image
• TIFF original image

https://doi.org/10.1371/journal.pone.0271284.g001

QCI levels.

Level 1 included countries from all GBD super-regions: Central Europe, Eastern Europe, and central Asia; High income; Latin America and Caribbean; North Africa and the Middle East; South Asia; Southeast Asia, East Asia, and Oceania; and Sub-Saharan Africa. High income; Latin America and Caribbean; Southeast Asia, East Asia, and Oceania; and Sub-Saharan Africa had varied age-standardized QCI levels, spanning from Level 5 to Level 1. Among GBD super-regions, South Asia had the most improvement in QCI score ( Fig 1 and S5 Table ).

SDI levels.

Age-standardized QCI of high SDI countries was 82.9 (Level 2) in 1990, which increased by 12.0% to 92.9 (Level 1) in 2019. The QCI of low SDI countries was 65.0 (Level 5) in 1990, which increased by 76.9 (Level 2) in 2019. There was heterogeneity among the QCI level of countries with the same SDI level: i.e., the United Kingdom (76.8) and Singapore (98.5). The QCI level of countries with high or high-middle SDI varied from Level 5 to Level 1. No countries with middle, low-middle, or low SDI had a Level 1 QCI score, except for Nepal ( Fig 2 and S5 Table ).

https://doi.org/10.1371/journal.pone.0271284.g002

Age pattern for quality of care index

QCI typically decreases as people age, and inequity exists between age groups. However, there was a considerable gap between High SDI countries and Low SDI countries. In 2019, the QCI in high SDI countries was >90 for all ages. QCI remained >75 for ages <49 in Low-SDI countries and then decreased to its dew point at less than 75 for ages 50–54 ( Fig 3 ).

https://doi.org/10.1371/journal.pone.0271284.g003

Gender disparity ratio

GDR was calculated by dividing the age-standardized QCI of women by that of men: GDR closer to one indicated better equality. In 2019, the overall average of age-standardized GDR was 1.01 globally, which indicated that QCI was similar among women and men. Of 204 countries, the GDR of 100 countries ranged from 0.97 to 1.03, which was considered equality among both genders. Fifteen countries had GDR equal to one. Guinea-Bissau with GDR equal to 1.3 had the worst quality of care for men comparing with women in 2019. On the other hand, Honduras, Kiribati, and Pakistan, with GDR equal to 0.15, 0.71, and 0.78, had the highest gender disparity in favor of men in 2019 ( S6 Table ).

The gap between QCI of women and men has become narrower from 1990 to 2019. As opposed to High SDI countries, there was a significant gap between the GDR of older age groups and younger age groups in Low-SDI countries in 2019. In younger age groups, women had higher QCI than men, which was then conversed for middle age groups in favor of men, and then again in favor of women among older adults ( Fig 4 ).

https://doi.org/10.1371/journal.pone.0271284.g004

The global age-standardized QCI improved from 72.6 in 1990 to 83.2 in 2019, and nearly all countries and territories increased their index during this time. Singapore, Turkey, Japan, the Republic of Korea, and the United States of America had the highest QCI in 2019. Although higher SDI countries generally had higher QCI, there was significant heterogeneity for countries at similar SDI. Notwithstanding, the gap between the highest and lowest QCI was not bridged in the last three decades.

High-income Asia pacific had the highest QCI, both in 1990 and 2019. Interestingly, the prevalence of gastric cancer was highest in the high-income Asia Pacific [ 31 ]. In this region, Singapore, Japan, and the Republic of Korea had the highest QCI in 1990 and 2019. As a gastric cancer prevalent country, Japan implemented various screening programs for PUD and gastric cancer [ 32 ], which have been most successful in decreasing its prevalence [ 31 ]. Over the past years, Japan has been following a screen and treat approach, especially for adolescents, since Helicobacter pylori are mainly acquired during childhood [ 33 ]. In contrast to the Republic of Korea, QCI in the Democratic People’s Republic of Korea decreased in the last three decades, highlighting the wide gap in their economic development [ 34 ].

Although younger age groups had significantly higher QCI both in high and low SDI countries, the inequities among age groups decreased during 1990–2019. PUD in the elderly needs sustained attention since its presentation is insidious compared to younger patients; thus, diagnosis is delayed [ 35 ]. Older age is also associated with a higher incidence of Helicobacter pylori-associated and non-Helicobacter pylori-associated PUD due to the dramatic increase in the prescription of antithrombotic agents and non-steroidal anti-inflammatory drugs (NSAIDs) [ 36 ]. The mortality of bleeding peptic ulcers remains higher among patients over 60 years of age, especially those over 80, despite previous advances in pharmacological and endoscopic treatment [ 37 ]. PUD diagnosis and treatment approaches could be incredibly costly for low SDI countries, which could become a predisposing factor for favoring resource allocation for younger age groups.

The global GDR was close to one, indicating that QCI was similar among women and men. In addition, the GDR of nearly half of the countries ranged from 0.97 to 1.03. Although GDR could bring some insights towards seeing the big picture, it could also become misleading. In case the QCI of both women and men is low, the ratio would seem satisfactory. Higher QCI among women could be due to increased PUD complications among men [ 38 ]. Nevertheless, the novel emerging evidence on the predisposing factors of complicated or non-complicated PUD would suggest that the witnessed inequities among age groups across various countries could be due to otherwise neglected factors such as the number of household members [ 39 ]. Thus, further research is required to enhance the current understanding of the existing inequities to help bridge the gaps among various groups, especially in low and low-middle income countries.

From 1990 to 2019, there has been a 31% reduction in the global age-standardized prevalence rate of PUD, 31% in age-standardized incidence rate, and 59% in age-standardized mortality rate. Other studies also showed a sharp decreasing trend in the prevalence, incidence, and mortality associated with PUD over the past 2–3 decades [ 2 , 4 ]. The decline in the incidence and prevalence of PUD coincides with the decline in the prevalence of Helicobacter pylori. However, preventing factors like using medications that decrease gastric acid secretion and predisposing factors like smoking and the availability of non-steroidal, anti-inflammatory drugs need to be taken into account [ 40 ].

This study also highlights the considerable existing heterogeneity across the globe regarding the changes in prevalence, incidence, and mortality of PUD. While the age-standardized mortality rate due to PUD has decreased by 69% in high-SDI countries, low and low-middle SDI countries remain to have the highest age-standardized PUD mortality rate despite previous endeavors. The reasons for the witnessed heterogeneity could be larger family size, low socioeconomic status, overcrowding, poor sanitation, having an infected sibling, growth retardation, and nutritional deficiencies, particularly iron-deficiency anemia in low SDI countries [ 41 , 42 ]. The witnessed gaps and inequities call for concerted efforts to lessen the burden of PUD in areas with limited resources. Given the level of technology, expenses, and the expertise required for complications management of PUD, its early detection and prevention seem feasible and cost-effective [ 43 ]. However, further research is required to determine the most suitable strategies for early detection, treatment, and follow-up based on available resources.

Strengths and limitations

QCI combined mortality to incidence ratio [ 44 ], DALYs to prevalence ratio [ 45 ], prevalence to incidence ratio [ 46 ], and YLLs to YLDs ratio [ 47 ] into a single index, aiming to demonstrate the quality of care among countries [ 9 – 11 , 28 , 47 – 49 ]. Although QCI does not reflect all the aspects of the quality of services among healthcare systems, it could be used as a proxy for comparing various countries. The review of the existing literature also confirmed that the current situation of PUD on a global scale and its time trends during 1990–2019 mainly were consistent with the picture, as shown via QCI [ 3 , 4 , 27 , 50 ]. In addition, it showed an acceptable correlation with the HAQ Index for PUD. The advantage of QCI is that, unlike HAQ Index, it could be used to present inequities among both sexes, age groups, and in all the seven GBD super-regions and 21 regions. QCI combined mortality to incidence ratio [ 44 ], DALYs to prevalence ratio [ 45 ], prevalence to incidence ratio [ 46 ], and YLLs to YLDs ratio [ 47 ], into a single index, aiming to demonstrate the quality of care among countries [ 9 – 11 , 28 , 47 – 49 ]. Although QCI does not reflect all the aspects of the quality of services among healthcare systems, it could be used as a proxy for comparing various countries. The review of the existing literature also confirmed that the current situation of PUD on a global scale and its time trends during 1990–2019 was mainly were mostly consistent with the picture, as shown via QCI [ 3 , 4 , 27 , 50 ]. In addition, it showed an acceptable correlation with the HAQ Index for PUD. The advantage of QCI is that, unlike HAQ Index, it could be used to present inequities among both sexes, age groups, and in all the seven GBD super-regions and 21 regions.

Moreover, we used the estimates of GBD 2019, while the latest published HAQ Index used the data of GBD 2016 [ 28 ]. However, QCI does not currently capture subnational inequalities, and future efforts with a better geospatial resolution on sub-national levels need to be prioritized. Despite using as many data sources as possible, the GBD study includes estimations based on the predictive covariates in locations with scarce data sources. Since the data of this study were derived from the GBD study, the limitations experienced in GBD estimations also apply to this study [ 51 ]. Among risk factors of PUD, smoking was the only risk factor with sufficient data to be modeled in the GBD study 2019. In this study, PCA was used to generate QCI, a mathematical method [ 52 ]. GBD utilizes statistical methods to estimate the burden measures, i.e. DALYs, YLLs, YLDs, death, incidences, and prevalence. Nevertheless, PCA did not allow us to present any uncertainty values; thus, the study does not report confidence or uncertainty intervals. Despite its limitations, the current study could show the big picture of the current inequities regarding PUD management based on geographical distribution, sex, and age groups to empower policymakers in making well-informed decisions. Moreover, we used the estimates of GBD 2019, while the latest published HAQ Index used the data of GBD 2016 [ 28 ]. However, QCI does not currently capture subnational inequalities, and future efforts with a better geospatial resolution on sub-national levels need to be prioritized. Despite using as many data sources as possible, the GBD study includes estimations based on the predictive covariates in locations with scarce data sources. Since the data of this study were derived from the GBD study, the limitations experienced in GBD estimations also apply to this study [ 51 ]. Among risk factors of PUD, smoking was the only risk factor with sufficient data to be modeled in the GBD study 2019. Unfortunately In this study, PCA was used to generate QCI, a mathematical method [ 52 ]. GBD utilizes statistical methods to estimate the burden measures, i.e. DALYs, YLLs, YLDs, death, incidences, and prevalence. Nevertheless, PCA did not allow us to present any uncertainty values; thus, the study does not report confidence or uncertainty intervals limited statistical and computational resources hindered calculating the confidence interval for all estimated indices and significant values in this study. Despite its limitations, the current study could be used for showing show the big picture of the current inequities regarding PUD management based on geographical distribution, sex, and age groups to empower policymakers towards in making well-informed decisions.

Conclusions

QCI of PUD improved dramatically during 1990–2019 worldwide. There are still significant heterogeneities among countries on different and similar SDI levels. Given the inequities among various age groups and both sexes, there is still room for improvement for QCI and bridging the inequity gaps. The prosperous countries in this regard need to be introduced as role models, and their plans be implemented towards a sustained reduction of age-standardized death rates from the causes amenable to personal health care.

Supporting information

S1 table. data sources of gbd study 2019 for peptic ulcer disease..

https://doi.org/10.1371/journal.pone.0271284.s001

S2 Table. Mixed-effect regression analysis to assess the validation of QCI for PUD.

https://doi.org/10.1371/journal.pone.0271284.s002

S3 Table. Prevalence, incidence, and mortality of peptic ulcer disease among countries in 1990 and 2019.

https://doi.org/10.1371/journal.pone.0271284.s003

S4 Table. Changes in prevalence, incidence, and mortality of peptic ulcer disease among countries from 1990 to 2019.

https://doi.org/10.1371/journal.pone.0271284.s004

S5 Table. Age-standardized quality of care index and its levels of countries based on GBD super regions, regions, and SDI in 1990 and 2019.

* Locations were sorted by countries’ QCI in 2019.

https://doi.org/10.1371/journal.pone.0271284.s005

S6 Table. Gender disparity ratio of countries in 1990 and 2019.

* Locations were sorted by countries’ GDR in 2019.

https://doi.org/10.1371/journal.pone.0271284.s006

Acknowledgments

The authors sincerely thank all the collaborators who contributed to this study at Non-Communicable Diseases Research Center (NCDRC) and Endocrinology and Metabolism Research Institute (EMRI) at Tehran University of Medical Sciences, Tehran, Iran.

Ethics approval statement

The study data were initially derived from the Global Burden of Disease study, Institute for Health Metrics and Evaluation, which abides by relevant guidelines and regulations. Data from the GBD study are freely available to researchers and policymakers [ 53 ]. Notably, the first author and the corresponding author were collaborators of the GBD study. This study was approved by the institutional review board of Endocrinology and Metabolism Research Institute at Tehran University of Medical Sciences (IR.TUMS.EMRI.REC.1400.016).

• View Article
• PubMed/NCBI
• Google Scholar
• 8. Health system performance comparison. An agenda for policy, information and research (2013). 2017 [cited 30 Aug 2020]. Available: https://www.euro.who.int/en/about-us/partners/observatory/publications/studies/health-system-performance-comparison.-an-agenda-for-policy ,-information-and-research-2013
• 21. Frequently Asked Questions | Institute for Health Metrics and Evaluation. [cited 16 May 2022]. Available: https://www.healthdata.org/gbd/faq
• 25. VizHub—GBD Results. [cited 22 May 2022]. Available: https://vizhub.healthdata.org/gbd-results/
• 52. Johnson RA, Wichern DW. Applied multivariate statistical analysis. Pearson London, UK:; 2014.
• 53. GBD Data | Institute for Health Metrics and Evaluation. [cited 14 Jun 2021]. Available: http://www.healthdata.org/gbd/data

• - Google Chrome

Intended for healthcare professionals

• My email alerts
• BMA member login
• Username * Password * Forgot your log in details? Need to activate BMA Member Log In Log in via OpenAthens Log in via your institution

Search form

• Advanced search
• Search responses
• Search blogs

Peptic ulcer disease

• Related content
• Peer review
• Emma Sverdén , upper gastrointestinal surgeon 1 2 ,
• Lars Agréus , general practitioner , professor 3 4 ,
• Jason M Dunn , gastroenterologist 5 ,
• Jesper Lagergren , upper gastrointestinal surgeon, professor 1 5
• 1 Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
• 2 Department of Upper Gastrointestinal Surgery, South Hospital, Stockholm, Sweden
• 3 Division of Family Medicine and Primary Care, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
• 4 The University of Newcastle, Australia
• 5 School of Cancer and Pharmaceutical Sciences, King’s College London, and Guy’s and St Thomas’ NHS Foundation Trust, UK
• Correspondence to emma.s.eklund{at}gmail.com

What you need to know

More than 90% of duodenal ulcers are linked to H pylori infection; eradication therapy with antibiotics and proton pump inhibitors is the mainstay of treatment

A “test and treat” strategy for H pylori infection is appropriate in patients under 60 with suspected peptic ulcer disease who have no complications

Proton pump inhibitors are important in the prevention and treatment of peptic ulcer disease, but avoid their use without clear indications, and re-evaluate patients on long-term treatment

Gastric ulcers are followed up with endoscopy until healed to rule out malignancy

Urgently refer patients with complications such as bleeding, perforation, or penetration to an emergency unit

Peptic ulcer disease presents with gastrointestinal symptoms similar to dyspepsia and can be difficult to distinguish clinically. It can have potentially serious complications such as bleeding or perforation, with a high risk of mortality. 1 Optimal treatment with proton pump inhibitors (PPIs) facilitates healing and can prevent complications and recurrence.

Observational studies and surveys among healthcare providers report that adherence to evidence based treatment guidelines is often poor. 2 3 4 5 6 7 8 9 This results in inadequate treatment and overuse of PPIs. Increasingly, antibiotic resistance has affected the choice of eradication regimen for Helicobacter pylori infection, the main risk factor. In this Clinical Update, we review the epidemiology and management of peptic ulcer disease for non-specialists to guide prompt diagnosis and appropriate treatment.

What is peptic ulcer disease?

Peptic ulcer disease is often defined as a mucosal break greater than 3-5 mm in the stomach or duodenum with a visible depth. It is therefore an endoscopic diagnosis in contrast to dyspepsia, which is a clinical diagnosis based on symptoms alone. Peptic ulcer disease results from an imbalance between factors that protect the mucosa of the stomach and duodenum, and factors that cause damage to it (fig 1). …

Log in using your username and password

BMA Member Log In

If you have a subscription to The BMJ, log in:

• Need to activate
• Log in via institution
• Log in via OpenAthens

Log in through your institution

Subscribe from £184 *.

Subscribe and get access to all BMJ articles, and much more.

* For online subscription

Access this article for 1 day for: £33 / $40 / €36 ( excludes VAT )

You can download a PDF version for your personal record.

Buy this article

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• Review Article
• Published: 01 February 2006

Peptic ulcer disease today

• Yuhong Yuan 1 ,
• Ireneusz T Padol 1 &
• Richard H Hunt 2  

Nature Clinical Practice Gastroenterology & Hepatology volume  3 ,  pages 80–89 ( 2006 ) Cite this article

8970 Accesses

145 Citations

12 Altmetric

Metrics details

Over the past few decades, since the introduction of histamine H 2 -receptor antagonists, proton-pump inhibitors, cyclo-oxygenase-2-selective anti-inflammatory drugs (coxibs), and eradication of Helicobacter pylori infection, the incidence of peptic ulcer disease and ulcer complications has decreased. There has, however, been an increase in ulcer bleeding, especially in elderly patients. At present, there are several management issues that need to be solved: how to manage H. pylori infection when eradication failure rates are high; how best to prevent ulcers developing and recurring in nonsteroidal anti-inflammatory drug (NSAID) and aspirin users; and how to treat non-NSAID, non- H. pylori -associated peptic ulcers. Looking for H. pylori infection, the overt or surreptitious use of NSAIDs and/or aspirin, and the possibility of an acid hypersecretory state are important diagnostic considerations that determine the therapeutic approach. Combined treatment with antisecretory therapy and antibiotics for 1–2 weeks is the first-line choice for H. pylori eradication therapy. For patients at risk of developing an ulcer or ulcer complications, it is important to choose carefully which anti-inflammatory drugs, nonselective NSAIDs or coxibs to use, based on a risk assessment of the patient, especially if the high-risk patient also requires aspirin. Testing for and eradicating H. pylori infection in patients is recommended before starting NSAID therapy, and for those currently taking NSAIDs, when there is a history of ulcers or ulcer complications. Understanding the pathophysiology and best treatment strategies for non-NSAID, non- H. pylori -associated peptic ulcers presents a challenge.

When diagnosing peptic ulcer disease, important considerations are detecting H. pylori infection, NSAID and/or aspirin use, and an acid hypersecretory state

The first-line choice for H. pylori eradication is combination treatment with antisecretory drugs and antibiotics for 1–2 weeks

For patients at risk of developing an ulcer or ulcer complications, the choice of anti-inflammatory drugs, nonselective or COX2-selective NSAIDs should be carefully made

Testing for and eradicating H. pylori infection is recommended before starting NSAIDs, in those taking NSAIDs who have a history of ulcers or ulcer complications

Understanding the pathophysiology and optimal treatment of non-NSAID, non- H. pylori associated peptic ulcers is an important focus for future research

This is a preview of subscription content, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

195,33 € per year

only 16,28 € per issue

Buy this article

• Purchase on Springer Link
• Instant access to full article PDF

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

Clinical factors associated with initial Helicobacter pylori eradication therapy: a retrospective study in China

Effectiveness of acid suppressants and other mucoprotective agents in reducing the risk of occult gastrointestinal bleeding in nonsteroidal anti-inflammatory drug users

Comparison of the management of Helicobacter pylori infection between the older and younger European populations

Gustavsson S and Nyren O (1989) Time trends in peptic ulcer surgery, 1956 to 1986. A nation-wide survey in Sweden. Ann Surg 210 : 704–709

CAS   PubMed   PubMed Central   Google Scholar  

Sach G (1997) Proton pump inhibitors and acid-related diseases. Pharmacotherapy 17 : 22–37

Google Scholar  

Sonnenberg A (1985) Geographic and temporal variations in the occurrence of peptic ulcer disease. Scand J Gastroenterol Suppl 110 : 11–24

CAS   PubMed   Google Scholar  

Sonnenberg A and Everhart JE (1996) The prevalence of self-reported peptic ulcer in the United States. Am J Public Health 86 : 200–205

Sandler RS et al . (2002) The burden of selected digestive diseases in the United States. Gastroenterology 122 : 1500–1511

PubMed   Google Scholar  

Yuan Y and Hunt RH (2006) Treatment of non-NSAID and non- H. pylori gastroduodenal ulcers and hypersecretory states. In Therapy of digestive disorders , edn 2, 315–336 (Eds Wolfe MM et al .) London, UK: Elsevier

Tummala S et al . (2004) Update on the immunologic basis of Helicobacter pylori gastritis. Curr Opin Gastroenterol 20 : 592–597

Dore MP and Graham DY (2000) Pathogenesis of duodenal ulcer disease: the rest of the story. Baillieres Best Pract Res Clin Gastroenterol 14 : 97–107

Laine L (1996) Nonsteroidal anti-inflammatory drug gastropathy. Gastrointest Endosc Clin N Am 6 : 489–504

Wolfe MM and Soll AH (1988) The physiology of gastric acid secretion. N Engl J Med 319 : 1707–1715

Marshall BJ and Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1 : 1311–1315

Marshall BJ et al . (1985) Pyloric Campylobacter infection and gastroduodenal disease. Med J Aust 142 : 439–444

Graham DY et al . (1988) Effect of age on the frequency of active Campylobacter pylori infection diagnosed by the 13 C urea breath test in normal subjects and patients with peptic ulcer disease. J Infect Dis 157 : 777–780

Xia HH et al . (2001) Reduction of peptic ulcer disease and Helicobacter pylori infection but increase of reflux esophagitis in western Sydney between 1990 and 1998. Dig Dis Sci 46 : 2716–2723

Perez-Aisa MA et al . (2005) Clinical trends in ulcer diagnosis in a population with high prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 21 : 65–72

Ford A et al . (2004) Eradication therapy for peptic ulcer disease in Helicobacter pylori positive patients. The Cochrane Database of Systematic Reviews . Issue 4, Art. No. CD003840.pub2

Laine L (2001) Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient. Gastroenterology 120 : 594–606

Weisman SM and Graham DY (2002) Evaluation of the benefits and risks of low-dose aspirin in the secondary prevention of cardiovascular and cerebrovascular events. Arch Intern Med 162 : 2197–2202

Niv Y et al . (2005) Endoscopy in asymptomatic minidose aspirin consumers. Dig Dis Sci 50 : 78–80

Slattery J et al . (1995) Risks of gastrointestinal bleeding during secondary prevention of vascular events with aspirin—analysis of gastrointestinal bleeding during the UK-TIA trial. Gut 37 : 509–511

Lanas A et al . (2000) Nitrovasodilators, low-dose aspirin, other nonsteroidal antiinflammatory drugs, and the risk of upper gastrointestinal bleeding. N Engl J Med 343 : 834–839

Silverstein FE et al . (2000) Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study. A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 284 : 1247–1255

Bombardier C et al . (2000) Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 343 : 1520–1528

Hunt RH et al . (2003) The gastrointestinal safety of the COX-2 selective inhibitor etoricoxib assessed by both endoscopy and analysis of upper gastrointestinal events. Am J Gastroenterol 98 : 1725–1733

Schnitzer TJ et al . (2004) Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET) reduction in ulcer complications randomised controlled trial. Lancet 364 : 665–674

Huang JQ et al . (2002) Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis. Lancet 359 : 14–22

Lanas A et al . (2002) Helicobacter pylori increases the risk of upper gastrointestinal bleeding in patients taking low-dose aspirin. Aliment Pharmacol Ther 16 : 779–786

Talley NJ et al . (2005) American Gastroenterology Association technical review on the evaluation of dyspepsia. Gastroenterology 129 : 1756–1780

Ford AC et al . (2005) Helicobacter pylori 'test and treat' or endoscopy for managing dyspepsia: an individual patient data meta-analysis. Gastroenterology 128 : 1838–1844

Vakil N and Vaira D (2004) Non-invasive tests for the diagnosis of infection. Rev Gastroenterol Disord 4 : 1–6

Perri F et al . (1995) The influence of isolated doses of drugs, feeding and colonic bacterial ureolysis on urea breath test results. Aliment Pharmacol Ther 9 : 705–709

Prince MI et al . (1999) The CLO test in the UK: inappropriate reading and missed results. Eur J Gastroenterol Hepatol 11 : 1251–1254

Bilardi C et al . (2002) Stool antigen assay (HpSA) is less reliable than urea breath test for post-treatment diagnosis of Helicobacter pylori infection. Aliment Pharmacol Ther 16 : 1733–1738

Malfertheiner P et al . (2002) Current concepts in the management of Helicobacter pylori infection—the Maastricht 2-2000 Consensus Report. Aliment Pharmacol Ther 16 : 167–180

Vallve M et al . (2002) Single vs. double dose of a proton pump inhibitor in triple therapy for Helicobacter pylori eradication: a meta-analysis. Aliment Pharmacol Ther 16 : 1149–1156

Calvet X et al . (2000) A meta-analysis of short versus long therapy with a proton pump inhibitor, clarithromycin and either metronidazole or amoxycillin for treating Helicobacter pylori infection. Aliment Pharmacol Ther 14 : 603–609

Lahaie RG and Gaudreau C (2000) Helicobacter pylori antibiotic resistance: trends over time. Can J Gastroenterol 14 : 895–899

Laine L (2003) Is it time for quadruple therapy to be first line? Can J Gastroenterol 17 (Suppl B): 33B–35B

Gisbert JP and Pajares JM (2002) Review article: Helicobacter pylori 'rescue' regimen when proton pump inhibitor-based triple therapies fail. Aliment Pharmacol Ther 16 : 1047–1057

Furuta T et al . (2003) Therapeutic impact of CYP2C19 pharmacogenetics on proton pump inhibitor-based eradication therapy for Helicobacter pylori . Methods Find Exp Clin Pharmacol 25 : 131–143

Padol S et al . (2005) The effect of CYP2C19 polymorphism on H. pylori eradication rates with PPI dual and triple first line therapies—a meta-analysis [abstract #T970]. Gastroenterology 128 (Suppl 2): A430

Leodolter A et al . (2001) A meta-analysis comparing eradication, healing and relapse rates in patients with Helicobacter pylori -associated gastric or duodenal ulcer. Aliment Pharmacol Ther 15 : 1949–1958

Gisbert JP et al . (2004) H. pylori eradication therapy vs. antisecretory non-eradication therapy (with or without long-term maintenance antisecretory therapy) for the prevention of recurrent bleeding from peptic ulcer. The Cochrane Database of Systematic Reviews , Issue 2, Art. No. CD004062.pub2

Arkkila PE et al . (2005) Helicobacter pylori eradication as the sole treatment for gastric and duodenal ulcers. Eur J Gastroenterol Hepatol 17 : 93–101

Gisbert JP and Pajares JM (2005) Systematic review and meta-analysis: is 1-week proton pump inhibitor-based triple therapy sufficient to heal peptic ulcer? Aliment Pharmacol Ther 21 : 795–804

Ohara T et al . (2004) Usefulness of proton pump inhibitor (PPI) maintenance therapy for patients with H. pylori -negative recurrent peptic ulcer after eradication therapy for H. pylori : pathophysiological characteristics of H. pylori -negative recurrent ulcer scars and beyond acid suppression by PPI. Hepatogastroenterology 51 : 338–342

Lai KC et al . (2002) Lansoprazole for the prevention of recurrences of ulcer complications from long-term low-dose aspirin use. N Engl J Med 346 : 2033–2038

Yeomans ND (1988) New data on healing of nonsteroidal anti-inflammatory drug-associated ulcers and erosions. Omeprazole NSAID Steering Committee. Am J Med 104 : 56S–61S

Pilotto A et al . (2004) Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 20 : 1091–1097

Lanas A (2004) Economic analysis of strategies in the prevention of non-steroidal anti-inflammatory drug-induced complications in the gastrointestinal tract. Aliment Pharmacol Ther 20 : 321–331

Rostom A et al . (2002) Prevention of NSAID-induced gastroduodenal ulcers. The Cochrane Database of Systematic Reviews , Issue 4, Art. No. CD002296.pub2

Goldstein JL et al . (2004) Ulcer recurrence in high-risk patients receiving nonsteroidal anti-inflammatory drugs plus low-dose aspirin: results of a post hoc subanalysis. Clin Ther 26 : 1637–1643

Dubois RW et al . (2004) Guidelines for the appropriate use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2-specific inhibitors and proton pump inhibitors in patients requiring chronic anti-inflammatory therapy. Aliment Pharmacol Ther 19 : 197–208

Chan FK et al . (2004) Celecoxib versus diclofenac plus omeprazole in high-risk arthritis patients: results of a randomized double-blind trial. Gastroenterology 127 : 1038–1043

Hunt RH et al . (2002) Recommendations for the appropriate use of anti-inflammatory drugs in the era of the coxibs: defining the role of gastroprotective agents. Can J Gastroenterol 16 : 231–240

Lohmander LS et al . (2005) A randomised, placebo controlled, comparative trial of the gastrointestinal safety and efficacy of AZD3582 versus naproxen in osteoarthritis. Ann Rheum Dis 64 : 449–456

Fiorucci S et al . (2003) Gastrointestinal safety of NO-aspirin (NCX-4016) in healthy human volunteers: a proof of concept endoscopic study. Gastroenterology 124 : 600–607

Bias P et al . (2004) The gastrointestinal tolerability of the LOX/COX inhibitor, licofelone, is similar to placebo and superior to naproxen therapy in healthy volunteers: results from a randomized, controlled trial. Am J Gastroenterol 99 : 611–618

Pounder RE (2002) Helicobacter pylori and NSAIDs—the end of the debate? Lancet 359 : 3–4

Hunt RH and Bazzoli F (2004) Review article: should NSAID/low-dose aspirin takers be tested routinely for H. pylori infection and treated if positive? Implications for primary risk of ulcer and ulcer relapse after initial healing. Aliment Pharmacol Ther 19 (Suppl 1): 9–16

Vergara M et al . (2005) Meta-analysis: role of Helicobacter pylori eradication in the prevention of peptic ulcer in NSAID users. Aliment Pharmacol Ther 21 : 1411–1418

Chan FK et al . (2005) NSAID-induced peptic ulcers and Helicobacter pylori infection: implications for patient management. Drug Saf 28 : 287–300

Giral A et al . (2004) Effect of Helicobacter pylori eradication on anti-thrombotic dose aspirin-induced gastroduodenal mucosal injury. J Gastroenterol Hepatol 19 : 773–777

Chan FK et al . (2001) Preventing recurrent upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 344 : 967–973

MacDonald TM et al . (1997) Association of upper gastrointestinal toxicity of non-steroidal anti-inflammatory drugs with continued exposure: a cohort study. BMJ 315 : 1333–1337

Quan C and Talley NJ (2002) Management of peptic ulcer disease not related to Helicobacter pylori or NSAIDs. Am J Gastroenterol 97 : 2950–2961

Sprung DJ and Apter MN (1998) What is the role of Helicobacter pylori in peptic ulcer and gastric cancer outside the big cities? J Clin Gastroenterol 26 : 60–63

Jyotheeswaran S et al . (1998) Prevalence of Helicobacter pylori in peptic ulcer patients in greater Rochester, NY: is empirical triple therapy justified? Am J Gastroenterol 93 : 574–578

Nishikawa K et al . (2000) Non- Helicobacter pylori and non-NSAID peptic ulcer disease in the Japanese population. Eur J Gastroenterol Hepatol 12 : 635–640

Leontiadis GI et al . (2005) Systematic review and meta-analysis of proton pump inhibitor therapy in peptic ulcer bleeding. BMJ 330 : 568

PubMed   PubMed Central   Google Scholar  

Bardhan KD (1993) Is there any acid peptic disease that is refractory to proton pump inhibitors? Aliment Pharmacol Ther 7 (Suppl 1): 13–24

Lanas AI et al . (1995) Risk factors associated with refractory peptic ulcers. Gastroenterology 109 : 1124–1133

Lu H et al . (2005) Duodenal ulcer promoting gene of Helicobacter pylori . Gastroenterology 128 : 833–848

Download references

Author information

Authors and affiliations.

research associates Division of Gastroenterology, McMaster University, Health Science Centre, Hamilton, ON, Canada

Yuhong Yuan & Ireneusz T Padol

Professor of Medicine in the Division of Gastroenterology, McMaster University, Health Science Centre, Hamilton, ON, Canada

Richard H Hunt

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to Richard H Hunt .

Ethics declarations

Competing interests.

Richard H Hunt is or recently has been a consultant and/or investigator and/or speaker for the following pharmaceutical companies: Abbott, Allergan, Altana, AstraZeneca, Axcan, Merck, MerckFrosst, Merckle, Negma, Novartis, Pfizer, Proctor & Gamble and TAP.

Rights and permissions

Reprints and permissions

About this article

Cite this article.

Yuan, Y., Padol, I. & Hunt, R. Peptic ulcer disease today. Nat Rev Gastroenterol Hepatol 3 , 80–89 (2006). https://doi.org/10.1038/ncpgasthep0393

Download citation

Received : 16 August 2005

Accepted : 06 December 2005

Issue Date : 01 February 2006

DOI : https://doi.org/10.1038/ncpgasthep0393

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

This article is cited by

Caffeic acid phenethyl ester attenuates indomethacin-induced gastric ulcer in rats.

• Thikryat Neamatallah

Naunyn-Schmiedeberg's Archives of Pharmacology (2024)

Identification of chiral lansoprazole drugs using THz fingerprint spectroscopy

Chemical Papers (2023)

Cembranoids from the Red Sea soft coral Sarcophyton glaucum protect against indomethacin-induced gastric injury

• Nahed O. Bawakid
• Hajer S. Alorfi
• Walied M. Alarif

Naunyn-Schmiedeberg's Archives of Pharmacology (2023)

Therapeutic approach of adipose-derived mesenchymal stem cells in refractory peptic ulcer

• Mahshid Saleh
• Amir Ali Sohrabpour
• Amir Abbas Vaezi

Stem Cell Research & Therapy (2021)

Association of Helicobacter pylori vacA genotypes and peptic ulcer in Iranian population: a systematic review and meta-analysis

• Masoud Keikha
• Mohammad Ali-Hassanzadeh
• Mohsen Karbalaei

BMC Gastroenterology (2020)

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Disclaimer: Early release articles are not considered as final versions. Any changes will be reflected in the online version in the month the article is officially released.

Volume 30, Number 8—August 2024

Research Letter

Persistence of influenza h5n1 and h1n1 viruses in unpasteurized milk on milking unit surfaces.

Suggested citation for this article

Examining the persistence of highly pathogenic avian influenza A(H5N1) from cattle and human influenza A(H1N1)pdm09 pandemic viruses in unpasteurized milk revealed that both remain infectious on milking equipment materials for several hours. Those findings highlight the risk for H5N1 virus transmission to humans from contaminated surfaces during the milking process.

Highly pathogenic avian influenza A(H5N1) virus was detected in US domestic dairy cattle in late March 2024, after which it spread to herds across multiple states and resulted in at least 3 confirmed human infections ( 1 ). Assessment of milk from infected dairy cows indicated that unpasteurized milk contained high levels of infectious influenza virus ( 2 ; L.C. Caserta et al., unpub. data, https://doi.org/10.1101/2024.05.22.595317 ). Exposure of dairy farm workers to contaminated unpasteurized milk during the milking process could lead to increased human H5 virus infections. Such infections could enable H5 viruses to adapt through viral evolution within humans and gain the capability for human-to-human transmission.

Figure 1 . Illustration of milking unit surfaces tested in a study of persistence of influenza H5N1 and H1N1 viruses in unpasteurized milk. Before attaching the milking unit (claw), a dairy worker disinfects...

The milking process is primarily automated and uses vacuum units, commonly referred to as clusters or claws, which are attached to the dairy cow teats to collect milk ( Figure 1 ) ( 3 ). However, several steps in the milking process require human input, including forestripping, whereby workers manually express the first 3–5 streams of milk from each teat by hand. Forestripping stimulates the teats for optimal milk letdown, improves milk quality by removing bacteria, and provides an opportunity to check for abnormal milk. The forestripping process can result in milk splatter on the floor of the milking parlor and surrounding equipment and production of milk aerosols.

After forestripping, each teat is cleaned and dried by hand before the claw is installed. During milking, a flexible rubber inflation liner housed within the stainless-steel shell of the claw opens to enable the flow of milk and closes to exert pressure on the teat to stop the flow of milk ( Figure 1 ). When the flow of milk decreases to a specific level, the claw automatically releases ( 3 ), at which point residual milk in the inflation liner could spray onto dairy workers, equipment, or the surrounding area. Of note, milking often takes place at human eye level; the human workspace is physically lower than the cows, which increases the potential for infectious milk to contact human workers’ mucus membranes. No eye or respiratory protection is currently required for dairy farm workers, but recommendations have been released ( 4 ).

Influenza virus persistence in unpasteurized milk on surfaces is unclear, but information on virus persistence is critical to understanding viral exposure risk to dairy workers during the milking process. Therefore, we analyzed the persistence of infectious influenza viruses in unpasteurized milk on surfaces commonly found in milking units, such as rubber inflation liners and stainless steel ( Figure 1 ).

For infectious strains, we used influenza A(H5N1) strain A/dairy cattle/TX/8749001/2024 or a surrogate influenza A(H1N1)pdm09 pandemic influenza virus strain, A/California/07/2009. We diluted virus 1:10 in raw unpasteurized milk and in phosphate-buffered saline (PBS) as a control. As described in prior studies ( 5 – 7 ), we pipetted small droplets of diluted virus in milk or PBS onto either stainless steel or rubber inflation liner coupons inside an environmental chamber. We then collected virus samples immediately (time 0) or after 1, 3, or 5 hours to detect infectious virus by endpoint titration using a 50% tissue culture infectious dose assay ( 7 ). To mimic environmental conditions within open-air milking parlors in the Texas panhandle during March–April 2024, when the virus was detected in dairy herds, we conducted persistence studies using 70% relative humidity.

Figure 2 . Viral titers in a study of persistence of influenza H5N1 and H1N1 viruses in unpasteurized milk on milking unit surfaces. A) Viral titers of bovine A(H5N1) virus diluted 1:10 in...

We observed that the H5N1 cattle virus remained infectious in unpasteurized milk on stainless steel and rubber inflation lining after 1 hour, whereas infectious virus in PBS fell to below the limit of detection after 1 hour ( Figure 2 , panel A). That finding indicates that unpasteurized milk containing H5N1 virus remains infectious on materials within the milking unit. To assess whether a less pathogenic influenza virus could be used as a surrogate to study viral persistence on milking unit materials, we compared viral decay between H5N1 and H1N1 in raw milk over 1 hour on rubber inflation liner and stainless-steel surfaces ( Figure 2 , panel B). The 2 viruses had similar decay rates on both surfaces, suggesting that H1N1 can be used as a surrogate for H5N1 cattle virus in studies of viral persistence in raw milk. Further experiments examining H1N1 infectiousness over longer periods revealed viral persistence in unpasteurized milk on rubber inflation liner for at least 3 hours and on stainless steel for at least 1 hour ( Figure 2 , panel C). Those results indicate that influenza virus is stable in unpasteurized milk and that influenza A virus deposited on milking equipment could remain infectious for >3 hours.

Taken together, our data provide compelling evidence that dairy farm workers are at risk for infection with H5N1 virus from surfaces contaminated during the milking process. To reduce H5N1 virus spillover from dairy cows to humans, farms should implement use of personal protective equipment, such as face shields, masks, and eye protection, for workers during milking. In addition, contaminated rubber inflation liners could be responsible for the cattle-to-cattle spread observed on dairy farms. Sanitizing the liners after milking each cow could reduce influenza virus spread between animals on farms and help curb the current outbreak.

Dr. Le Sage is a research assistant professor at the University of Pittsburgh Center for Vaccine Research, Pittsburgh, Pennsylvania, USA. Her research interests include elucidating the requirements for influenza virus transmission and assessing the pandemic potential of emerging influenza viruses.

Acknowledgments

We thank the Lakdawala lab members, Centers of Excellence for Influenza Research and Response (CEIRR) risk assessment pipeline meeting attendees, Rachel Duron, and Linsey Marr for useful feedback.

This project was funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under contract no. 75N93021C00015 and a National Institutes of Health award (no. UC7AI180311) from the National Institute of Allergy and Infectious Diseases supporting the operations of the University of Pittsburgh Regional Biocontainment Laboratory in the Center for Vaccine Research. H5N1 studies were performed in accordance with select agent permit no. 20230320-074008 at the University of Pittsburgh.

This article was preprinted at https://www.medrxiv.org/content/10.1101/2024.05.22.24307745v1 .

• Centers for Disease Control and Prevention . H5N1 bird flu: current situation summary [ cited 2024 Jun 13 ]. https://www.cdc.gov/flu/avianflu/avian-flu-summary.htm
• Burrough  ER , Magstadt  DR , Petersen  B , Timmermans  SJ , Gauger  PC , Zhang  J , et al. Highly pathogenic avian influenza A(H5N1) clade 2.3.4.4b virus infection in domestic dairy cattle and cats, United States, 2024. Emerg Infect Dis . 2024 ; 30 : 1335 – 43 . DOI PubMed Google Scholar
• Odorčić  M , Rasmussen  MD , Paulrud  CO , Bruckmaier  RM . Review: Milking machine settings, teat condition and milking efficiency in dairy cows. Animal . 2019 ; 13 ( S1 ): s94 – 9 . DOI PubMed Google Scholar
• Centers for Disease Control and Prevention . Avian influenza (bird flu): reducing risk for people working with or exposed to animals [ cited 2024 Jun 20 ]. https://www.cdc.gov/bird-flu/prevention/worker-protection-ppe.html
• Qian  Z , Morris  DH , Avery  A , Kormuth  KA , Le Sage  V , Myerburg  MM , et al. Variability in donor lung culture and relative humidity impact the stability of 2009 pandemic H1N1 influenza virus on nonporous surfaces. Appl Environ Microbiol . 2023 ; 89 : e0063323 . DOI PubMed Google Scholar
• Kormuth  KA , Lin  K , Qian  Z , Myerburg  MM , Marr  LC , Lakdawala  SS . Environmental persistence of influenza viruses is dependent upon virus type and host origin. MSphere . 2019 ; 4 : e00552 – 19 . DOI PubMed Google Scholar
• Kormuth  KA , Lin  K , Prussin  AJ II , Vejerano  EP , Tiwari  AJ , Cox  SS , et al. Influenza virus infectivity is retained in aerosols and droplets independent of relative humidity. J Infect Dis . 2018 ; 218 : 739 – 47 . DOI PubMed Google Scholar
• Figure 1 . Illustration of milking unit surfaces tested in a study of persistence of influenza H5N1 and H1N1 viruses in unpasteurized milk. Before attaching the milking unit (claw), a dairy worker...
• Figure 2 . Viral titers in a study of persistence of influenza H5N1 and H1N1 viruses in unpasteurized milk on milking unit surfaces. A) Viral titers of bovine A(H5N1) virus diluted 1:10...

Suggested citation for this article : Le Sage V, Campbell AJ, Reed DS, Duprex WP, Lakdawala SS. Persistence of influenza H5N1 and H1N1 viruses in unpasteurized milk on milking unit surfaces. Emerg Infect Dis. 2024 Aug [ date cited ]. https://doi.org/10.3201/eid3008.240775

DOI: 10.3201/eid3008.240775

Original Publication Date: June 24, 2024

1 These first authors contributed equally to this article.

Table of Contents – Volume 30, Number 8—August 2024

Please use the form below to submit correspondence to the authors or contact them at the following address:

Seema Lakdawala, Emory University School of Medicine, 1510 Clifton Rd, Rm 3121 Rollins Research Center, Atlanta, GA 30322, USA

Comment submitted successfully, thank you for your feedback.

There was an unexpected error. Message not sent.

Exit Notification / Disclaimer Policy

• The Centers for Disease Control and Prevention (CDC) cannot attest to the accuracy of a non-federal website.
• Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website.
• You will be subject to the destination website's privacy policy when you follow the link.
• CDC is not responsible for Section 508 compliance (accessibility) on other federal or private website.

Metric Details

Article views: 1945.

Data is collected weekly and does not include downloads and attachments. View data is from .

What is the Altmetric Attention Score?

The Altmetric Attention Score for a research output provides an indicator of the amount of attention that it has received. The score is derived from an automated algorithm, and represents a weighted count of the amount of attention Altmetric picked up for a research output.

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings
• My Bibliography
• Collections
• Citation manager

Save citation to file

Email citation, add to collections.

• Create a new collection
• Add to an existing collection

Add to My Bibliography

Your saved search, create a file for external citation management software, your rss feed.

• Search in PubMed
• Search in NLM Catalog
• Add to Search

Pressure ulcers: Prevention and management

Affiliations.

• 1 Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts. Electronic address: [email protected].
• 2 Department of Dermatology, Boston University School of Medicine, Boston, Massachusetts.
• PMID: 30664906
• DOI: 10.1016/j.jaad.2018.12.068

Prevention has been a primary goal of pressure ulcer research. Despite such efforts, pressure ulcers remain common in hospitals and in the community. Moreover, pressure ulcers often become chronic wounds that are difficult to treat and that tend to recur after healing. Especially given these challenges, dermatologists should have the knowledge and skills to implement pressure ulcer prevention strategies and to effectively treat pressure ulcers in their patients. This continuing medical education article focuses on pressure ulcer prevention and management, with an emphasis on the evidence for commonly accepted practices.

Keywords: chronic wounds; debridement; dressings; management; nutrition; pressure injury; pressure sore; pressure ulcer; prevention; repositioning; support surface; surgery; therapy; treatment; wound care; wound healing; wounds.

Copyright © 2019 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

PubMed Disclaimer

Similar articles

• Applying negative pressure therapy to deep pressure ulcers covered by soft necrotic tissue. Nakayama M. Nakayama M. Int Wound J. 2010 Jun;7(3):160-6. doi: 10.1111/j.1742-481X.2010.00667.x. Epub 2010 Apr 23. Int Wound J. 2010. PMID: 20455957 Free PMC article.
• Treatment of pressure ulcers: results of a study comparing evidence and practice. Helberg D, Mertens E, Halfens RJ, Dassen T. Helberg D, et al. Ostomy Wound Manage. 2006 Aug;52(8):60-72. Ostomy Wound Manage. 2006. PMID: 16896239
• Pressure ulcers: diagnostics and interventions aimed at wound-related complaints: a review of the literature. de Laat EH, Scholte op Reimer WJ, van Achterberg T. de Laat EH, et al. J Clin Nurs. 2005 Apr;14(4):464-72. doi: 10.1111/j.1365-2702.2004.01090.x. J Clin Nurs. 2005. PMID: 15807753 Review.
• Systematic reviews of wound care management: (3) antimicrobial agents for chronic wounds; (4) diabetic foot ulceration. O'Meara S, Cullum N, Majid M, Sheldon T. O'Meara S, et al. Health Technol Assess. 2000;4(21):1-237. Health Technol Assess. 2000. PMID: 11074391 Review.
• Pressure ulcers. Local wound care. Goode PS, Thomas DR. Goode PS, et al. Clin Geriatr Med. 1997 Aug;13(3):543-52. Clin Geriatr Med. 1997. PMID: 9227943 Review.
• Prevention of Postoperative Skin Disorders and Pressure Injuries in the Neurosurgical Park Bench Position Surgery: A Prospective Cohort Study. Hara K, Uemura T, Tachibana R, Kumashiro R, Yamaguchi M, Kawahara I, Fujioka M. Hara K, et al. Cureus. 2024 Apr 18;16(4):e58552. doi: 10.7759/cureus.58552. eCollection 2024 Apr. Cureus. 2024. PMID: 38765353 Free PMC article.
• Accelerated infected wound healing by probiotic-based living microneedles with long-acting antibacterial effect. Jin Y, Lu Y, Jiang X, Wang M, Yuan Y, Zeng Y, Guo L, Li W. Jin Y, et al. Bioact Mater. 2024 May 8;38:292-304. doi: 10.1016/j.bioactmat.2024.05.008. eCollection 2024 Aug. Bioact Mater. 2024. PMID: 38745591 Free PMC article.
• Differentiating Pressure Ulcer Risk Levels through Interpretable Classification Models Based on Readily Measurable Indicators. Vera-Salmerón E, Domínguez-Nogueira C, Sáez JA, Romero-Béjar JL, Mota-Romero E. Vera-Salmerón E, et al. Healthcare (Basel). 2024 Apr 27;12(9):913. doi: 10.3390/healthcare12090913. Healthcare (Basel). 2024. PMID: 38727470 Free PMC article.
• Prediction Pressure Ulcers in High Care Unit Patients: Evaluating Risk Factors and Predictive Scale Using a Prospective Cross-Sectional Study. Indraswari ADW, Aisyiyah U, Kurniawan K, Surboyo MDC. Indraswari ADW, et al. Avicenna J Med. 2024 Feb 27;14(1):39-44. doi: 10.1055/s-0043-1777420. eCollection 2024 Jan. Avicenna J Med. 2024. PMID: 38694142 Free PMC article.
• Effect of platelet-rich plasma combined with negative pressure wound therapy in treating patients with chronic wounds: A meta-analysis. Chen H, Xu TJ, Yu H, Zhu JL, Liu Y, Yang LP. Chen H, et al. Int Wound J. 2024 Apr;21(4):e14758. doi: 10.1111/iwj.14758. Int Wound J. 2024. PMID: 38629618 Free PMC article.
• Search in MeSH

Related information

• Cited in Books

LinkOut - more resources

Full text sources.

• Elsevier Science
• Ovid Technologies, Inc.
• MedlinePlus Health Information
• Citation Manager

NCBI Literature Resources

MeSH PMC Bookshelf Disclaimer

The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.

• SUGGESTED TOPICS
• The Magazine
• Newsletters
• Managing Yourself
• Managing Teams
• Work-life Balance
• The Big Idea
• Data & Visuals
• Reading Lists
• Case Selections
• HBR Learning
• Topic Feeds
• Account Settings
• Email Preferences

Research: Warehouse and Logistics Automation Works Better with Human Partners

• René de Koster

A recent study suggests that blending human labor with robotics leads to greater efficiency.

A study of automation usage in warehouse and logistics companies around the world suggests that blending human labor with robotics leads to greater efficiency than full automation alone. While scalable robotic systems can handle up to 1,000 tasks per hour, they often face limitations where additional robots don’t improve performance. Human-robot collaboration, employed by companies like DHL and CEVA, enhances productivity, reduces worker fatigue, and increases job satisfaction. The incremental approach of integrating human roles with automated systems not only keeps operations cost effective but also leverages human adaptability for continuous improvements.

In every sphere of business, the use of automation is growing. In warehouses and distribution, for instance, the worldwide market revenue for robotics automation is projected to grow from $7.91 billion in 2021 to more than $51 billion by 2030, according to one Statista forecast .

• RK René de Koster is a professor of logistics and operations management at Rotterdam School of Management, Erasmus University.
• DR Debjit Roy is an institute chair professor in the operations and decision sciences area at the Indian Institute of Management Ahmedabad, India.

Partner Center

• Share full article

Advertisement

Supported by

Guest Essay

What Happened to Stanford Spells Trouble for the Election

By Renée DiResta

Ms. DiResta is the former research director of the Stanford Internet Observatory, a unit of Stanford University that studies abuse of online platforms.

In 2020 the Stanford Internet Observatory, where I was until recently the research director, helped lead a project that studied election rumors and disinformation. As part of that work, we frequently encountered conspiratorial thinking from Americans who had been told the 2020 presidential election was going to be stolen.

The way theories of “the steal” went viral was eerily routine . First, an image or video, such as a photo of a suitcase near a polling place, was posted as evidence of wrongdoing. The poster would tweet the purported evidence, tagging partisan influencers or media accounts with large followings. Those accounts would promote the rumor, often claiming, “Big if true!” Others would join, and the algorithms would push it out to potentially millions more. Partisan media would follow.

If the rumor was found to be false — and it usually was — corrections were rarely made and even then, little noticed. The belief that “the steal” was real led directly to the events of Jan. 6, 2021.

Within a couple of years, the same online rumor mill turned its attention to us — the very researchers who documented it. This spells trouble for the 2024 election.

For us, it started with claims that our work was a plot to censor the right. The first came from a blog related to the Foundation for Freedom Online, the project of a man who said he “ran cyber” at the State Department. This person, an alt-right YouTube personality who’d gone by the handle Frame Game, had been employed by the State Department for just a couple of months .

Using his brief affiliation as a marker of authority, he wrote blog posts styled as research reports contending that our project, the Election Integrity Partnership, had pushed social media networks to censor 22 million tweets. He had no firsthand evidence of any censorship, however: his number was based on a simple tally of viral election rumors that we’d counted and published in a report after the election was over. Right-wing media outlets and influencers nonetheless called it evidence of a plot to steal the election, and their followers followed suit.

We are having trouble retrieving the article content.

Please enable JavaScript in your browser settings.

Thank you for your patience while we verify access. If you are in Reader mode please exit and  log into  your Times account, or  subscribe  for all of The Times.

Thank you for your patience while we verify access.

Already a subscriber?  Log in .

Want all of The Times?  Subscribe .

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• Adv Wound Care (New Rochelle)

Review of the Current Management of Pressure Ulcers

Tatiana v. boyko.

1 Hagey Laboratory for Pediatric Regenerative Medicine, Department of Surgery, Plastic and Reconstructive Surgery Division, Stanford University School of Medicine, Stanford, California.

2 Department of Surgery, University at Buffalo SUNY, Buffalo, New York.

Michael T. Longaker

3 Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California.

George P. Yang

4 Department of Surgery, Stanford University School of Medicine, Stanford, California.

5 Veterans Affairs Palo Alto Health Care System, Palo Alto, California.

Significance: The incidence of pressure ulcers is increasing due to our aging population and the increase in the elderly living with disability. Learning how to manage pressure ulcers appropriately is increasingly important for all professionals in wound care.

Recent Advances: Many new dressings and treatment modalities have been developed over the recent years and the goal of this review is to highlight their benefits and drawbacks to help providers choose their tools appropriately.

Critical Issues: Despite an increased number of therapies available on the market, none has demonstrated any clear benefit over the others and pressure ulcer treatment remains frustrating and time-consuming.

Future Directions: Additional research is needed to develop products more effective in prevention and treatment of pressure ulcers.

George P. Yang, MD, PhD

Scope and Significance

T he fastest growing segment of our population is those over 65 years of age, and there are increased rates of obesity, diabetes, and cardiovascular disease. 1 This combination of factors has resulted in more people needing assistance with activities of daily living due to decreased mobility. 2 A major morbidity of decreased mobility is development of a pressure ulcer. The treatment for pressure ulcers is lengthy and causes a significant financial burden on the healthcare system. In the United States, an estimated $11 billion dollars is spent on pressure ulcers yearly, with $500 to $70,000 being spent on a single wound. 3

Translational Relevance

Despite a number of new dressings and treatments available for the management of pressure ulcers, none has been demonstrated to have a significant benefit over the other. The basic principles of maintaining the wound clean and well perfused remain the hallmarks of therapy. A major target for new therapies would be finding approaches to decrease incidence among susceptible patients, especially given potential penalties in reimbursement for patients who do develop a pressure ulcer.

Clinical Relevance

The prevention and treatment of pressure ulcers are highly relevant to wound care professionals. These patients require prolonged course of treatment to fully heal their wounds. The biomedical burden is tremendous as noted above and healthcare expenditures on this problem are only rising. Penalties now imposed for hospital-acquired pressure ulcers mean we need greater knowledge about causation and prevention.

Pressure ulcers develop as a result of a combination of physiologic events and external conditions. The classic thinking of tissue ischemia induced by prolonged external pressure on tissue being the sole causative factor of pressure ulcer formation has been examined more systematically. Along with localized ischemia and reperfusion injury to tissues, impaired lymphatic drainage has been shown to contribute to injury as well. Compression prevents lymph fluid drainage, which causes increased interstitial fluid and waste build up and contributes to pressure ulcer development. Deformation of tissues has been shown to be a greater indicator of pressure ulcer formation than pressure exerted on tissues alone. 4 The time required to develop a pressure ulcer is dependent on many factors, including the patient's physiology and the degree of pressure and shear force placed on the tissue. 5 Pressure ulcers occur over predictable pressure points where bony protuberances are more likely to compress tissues when the patient is in prolonged contact with hard surfaces ( Fig. 1 ). 6 , 7 For patients unable to move themselves, such as intubated patients in the ICU, positional change every 2 hours has been widely accepted as effective prevention. 8 , 9 Surgeries longer than 4 hours on a standard OR table have been shown to increase the risk of pressure ulcer formation leading to the routine use of gel pads in areas of risk during prolonged surgery. 10

Illustration of locations of pressure ulcers in supine patients. To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/wound

Pressure ulcer formation is highly influenced by risk factors ( Table 1 ), including all conditions leading to immobility, decreased or lack of sensation, as well as malnutrition. 11 Extrinsic risk factors include being immobilized on a spinal board, OR table, or bed for prolonged periods of time, as well as poorly fitted medical devices in contact with patient tissues. Intrinsic risk factors such as diabetes, malnutrition, and smoking also increase the overall risk for pressure ulcers. The spinal cord injury patient population is at the highest risk (25–66%) of developing a pressure ulcer due to the combination of immobility and decreased sensation. A prospective study of spinal cord patients not only found that sacral and ischial pressure ulcers were very common (43% and 15%, respectively), as might be expected, but also noted that the second most common location was on the heel (19%). 12 , 13 Nursing home patients have a pressure ulcer prevalence of 11% and are most likely to develop pressure ulcers over the sacrum or heels. 14 , 15 Nursing home patients were also found to have contractures at a prevalence of 55%. 16 Contractures are caused by decreased elasticity of the tissue surrounding major joints, and the resulting lack of full mobility in the affected extremities significantly increases the risk of pressure ulcer formation. These data highlight how critical the need is to understand the physical, environmental, and medical risks for development of pressure ulcers in the individual patient to prevent them.

Intrinsic and extrinsic factors influencing the development of pressure ulcers

Risk Assessment

Assessing the risk for the development of pressure ulcers needs to be performed in all patients to institute appropriate prevention measures in those at risk. Risk should be assessed in all admitted patients as well as with any changes in mobility or medical conditions. Several risk assessment scales exist. The Norton scale scores the following five categories from a low of 1 to a high of 4: physical condition, mental condition, activity, mobility, and incontinence. A total score less than 14 indicates high risk for pressure ulcer development. 17 The Braden scale is similar giving up to four points in the categories of sensory perception, moisture, activity, mobility, nutrition, and friction with a higher score indicating lower risk. 18 The exact specific scale used is not as important as simply having regular risk assessment and exercising clinical judgment. 19

Prevention of pressure ulcer formation is directed at alleviating the risk factors for the individual patient, and is primarily focused on minimizing episodes of prolonged pressure either by placing appropriate padding at pressure points or by frequent patient repositioning. All patients using prosthetics or requiring a wheelchair for mobility should be appropriately fitted to ensure that the fit is correct and there is adequate padding. The fitting process should be repeated if there are any significant changes in weight or body habitus that can affect fit. Sweat, urine, and stool can lead to maceration of the skin and the initial skin breakdown can lead to a pressure ulcer if the skin is overlying a pressure point. 20 A significant focus for care of at-risk patients is keeping the skin clean and dry. Even with adequate padding, it is important to make routine positional changes as even relatively low pressures can cause a pressure ulcer with prolonged exposure. 5 , 21

Pressure mapping technologies have been developed to measure the amount of pressure placed on different parts of the sitting or reclining body. These technologies have been used to develop pressure-relieving wheelchair cushions and to study normal weight-shifting behavior. 22 These technologies were also used in determining that 30 degrees of wheelchair tilt is needed to relieve pressure from the ischial and sacral areas. 23 Their use in bed-bound patients has been limited but has great potential for determining pressure points at risk for ulceration and in determining the effect of pressure-relieving positions on established wounds.

Any patient who has been determined to be at risk for development of a pressure ulcer or who already has a pressure ulcer needs to have a plan for repositioning. The plan needs to be individually tailored for each patient to address his or her specific needs. Frequency of repositioning needs to take many factors into account, including the support surface for the patient, general medical condition, and goals of care. Clinicians need to be cognizant of the fact that repositioning itself can create shear forces on skin, and so, the fragility and condition of the patient's skin need to be part of the assessment for how frequently to reposition them. There are a variety of factors to take into account for how to reposition patients depending on whether the patient is supine, prone, or in a wheelchair. Of special note for patients in the acute hospital setting are medical devices. Care must be taken since inadvertent positioning of the device between the patient and the support surface can create a high-pressure zone. While repositioning, lifting instead of dragging patients reduces friction and shear forces on the skin and prevents skin damage. 5 Documentation of repositioning and regular skin condition assessment is key in determining early signs of pressure ulcer formation such as nonblanching erythema. System solutions such as electronic medical record programs, which prompt providers to document results of pressure ulcer screening every shift or day, are of great importance in diagnosing pressure ulcers early and preventing progression. 24

A variety of pads are available, which are designed to specifically cover pressure points such as the sacrum and heels as well as foam pads designed to wrap around body parts at risk (especially feet). 25 However, it is important to note that some pads can actually be detrimental. For example, supports with cutouts can have increased pressure at their edges. There are an equal number of mattress pads (egg crate mattresses, natural sheepskins, etc.) that serve to decrease pressure across a large surface area. 21 Silk-based fabrics have been shown to be superior in pressure ulcer prevention when compared to cotton-based fabrics due to a decrease in friction forces and subsequent damage to skin. 26

Finally, adequate nutrition is very important in preventing pressure ulcer formation. Nutritional supplementation can benefit patients with limited oral intake and enteral or parenteral feeding can become necessary in patients who are not able to safely ingest enough oral nutrients. Protein intake is especially important to maintain a positive nitrogen balance, and vitamin/mineral supplements are recommended in patients lacking a balanced diet. 27 Prealbumin is used as a laboratory test of short-term nutritional adequacy. Albumin is also useful, but its longer half-life means it is more reflective of nutrition over a long period of time.

Diagnosis and Assessment

Once a pressure ulcer is identified, staging and careful documentation of the size of the wound should be performed. Additional assessments of the ulcer include the location, surrounding skin condition, presence of tissue undermining and tunneling, and amount of exudate, odor, and tenderness. Pressure ulcers are classified into six categories ( Fig. 2 and Table 2 ). 7 , 28 Stage I describes intact skin with nonblanchable erythema. Stage II pressure ulcers have partial-thickness skin damage with possible blister formation, but no subcutaneous tissues visible. Stage III pressure ulcers have full-thickness skin loss with subcutaneous fat exposed but no muscles, bones, or tendons visible. Stage IV pressure ulcers have tissue loss with exposure of muscles, bones, tendons, or vital organs. A common hallmark of pressure ulcers is that the area of skin affected typically underestimates the amount of subcutaneous tissue involved. An unstageable pressure ulcer refers to a wound with an undetermined level of tissue injury because the entire base of the wound is covered by slough tissue and/or eschar. A deep tissue injury is a term recently proposed by the National Pressure Ulcer Advisory Panel (NPUAP) to describe a pressure wound that has tissue injury hidden below intact skin. 29 These wounds appear as deep bruises and have high potential for quick deterioration into a high-stage pressure ulcer.

Illustration of different stages of pressure ulcers. From left to right . Top diagram showing pressure ulcers Stage I: skin intact. Stage II: partial skin loss. Stage III: full-thickness skin loss, subcutaneous tissue exposed. Stage IV: muscle, tendon, bone or organs exposed. Bottom diagram showing unstageable pressure ulcer with tissue damage hidden from observer by eschar over entire wound. Deep tissue injury hidden from observer by intact skin appears as a bruise from above.

Table of different stages of pressure ulcers

The pressure ulcer scale for healing (PUSH tool) is a commonly used tool developed by the NPUAP, which grades pressure ulcers based on size of wound, wound bed tissue type, and exudate amount ( Table 3 ). 30 Another commonly used scale is the Bates-Jensen wound assessment tool which scores wounds based on size, depth, wound edges, tissue undermining, type and amount of necrotic tissue, type and amount of exudate, skin color, presence of edema, induration, granulation, and epithelialization. 31 Other similar tools such as the pressure sore status tool and Sessing scale are also of use. 32 It is more important to evaluate and monitor pressure ulcers in a close and consistent manner than the specific tool used to do so.

Pressure ulcer scale for healing (PUSH tool)

Copyright. NPUAP, 2003, reprinted with permission. Points are calculated per category and are added for a total score.

Further workup is sometimes warranted to define the extent of tissue involved. Because the area of skin breakdown is smaller than the total area affected, CT or MRI can be useful in defining the extent of the tissue involved and to determine whether osteomyelitis is present. 33 Wound cultures are not routinely performed, but should be considered with lack of ulcer healing and persistent evidence of infection. If a wound culture is to be performed, tissue culture is more informative than simply performing a swab of the wound. 5 Cultures showing more than 10 5 CFU/g are indicative of active tissue infection. In the extremities, the adequacy of perfusion should be accessed via the ankle–brachial index and vascular studies. 34

The mainstays of pressure ulcer treatment include offloading the offending pressure source, adequate drainage of any areas of infection, debridement of devitalized tissue, and regular wound care to support the healing process.

Pressure relief

The first step in management is offloading pressure from the wound site. All of the measures described above for prevention of pressure ulcers are equally applicable to their treatment. For bedridden patients, this means strict adherence to repositioning the patient regularly. Any methods to pad the area of the pressure ulcer should be instituted if not already in use. Beyond the usual onlays and pads, some patients may require specialty beds to aid in decreasing pressure. These beds typically use air to continually shift pressure points through a variety of approaches. 35 Even with these beds, patients still need to be repositioned regularly. For patients using prosthetics, they may need to go without them for a period of time to allow healing to occur. Any patient developing a pressure ulcer with a prosthetic should be refitted after they have healed to protect against future problems. Wheelchair-bound patients may need to have their mobility limited to allow healing. As with a prosthetic, the wheelchair should be reexamined for proper fit. 36

Infection control

An important part of the initial evaluation of a pressure ulcer is to determine if there is evidence of inadequately treated infection. The pressure ulcer should be examined for the presence of surrounding erythema or fluctuance. The presence of crepitus is more ominous and should result in an expeditious assessment for the possibility of a necrotizing soft tissue infection. If there is a determination that there is inadequate source control, the patient should be taken to the operating room for appropriate abscess drainage and debridement.

Some surgeons elect to treat the wound initially with locally applied antiseptics, including povidone iodine, silver sulfadiazine, hydrogen peroxide, or Dakin's solution (sodium hypochlorite). The theory is that these topical agents serve to kill bacteria in the pressure ulcer to allow for better healing. If these solutions are used, they should only be used in the short term as they can also retard wound healing in the long term through their cytotoxic effects. 37

Intravenous antibiotics should only be used in patients with significant cellulitis, or systemic signs and symptoms of infection, and should be stopped once those signs improve. A clean pressure ulcer, even with some necrotic debris, does not require intravenous antibiotics. Currently, most treatment protocols would recommend the use of intravenous antibiotics when there is evidence of osteomyelitis, but there is actually little evidence for its use. 38 , 39 Generally, osteomyelitis requires debridement of the infected bone and coverage with a well-perfused flap to allow it to heal. 40 Topical antibiotics have little role in the management of pressure ulcers.

Debridement

Debridement of devitalized tissue and biofilm and abscess drainage are necessary in the treatment of pressure ulcers. In cases where there is a significant amount of necrotic tissue, performing the initial debridement in the operating room allows for a more definitive procedure. Subsequent debridements are then more easily managed at the bedside. There are instances where significant debridement is not needed or should not be done. If there is a dry eschar without purulence or fluctuance, and minimal erythema, the eschar can be left in place. If there is little subcutaneous tissue under the eschar, as in the case of the heel, debridement should be done with care. When performing surgical debridement, tissue should be resected until healthy bleeding tissue is encountered. After the initial presentation, repeated debridements are often necessary as the extent of necrosis can be difficult to assess. 41

Other approaches to performing mechanical debridement include the use of acoustic energy in the form of ultrasound. Low-frequency ultrasound has been used to decrease bioburden of the wound and was shown to speed pressure ulcer healing. 5 Hydrotherapy, including whirlpool, pulsed lavage, and vibration therapy are occasionally used for pressure ulcer debridement. There are additional products that perform an autolytic or enzymatic debridement over time when no urgent need for debridement exists. 7 In cases where a patient cannot tolerate surgical debridement, there is an option of undergoing medical maggot debridement, in which maggots remove dead tissue, allowing the wound to heal. 42 The goal of all these approaches is to create a bed of well-granulated tissue throughout the ulcer cavity. Small well-granulated ulcers can heal with re-epithelialization, while skin grafting or a surgical flap may be necessary in larger ulcers.

Dressings and topical agents

Dressings should be chosen depending on the wound being treated ( Table 4 and Fig. 3 ). It should be noted that none of the dressings described below has been shown to have any superiority, and the choice of dressing should depend on the type of wound being treated. 43 Things to be considered include size, depth, shape and location of the wound, presence and volume of exudate, presence of tunneling and tissue undermining, type of tissue in wound bed, and surrounding skin condition. Skin surrounding the ulcer should be protected from excessive moisture and friction to prevent breakdown. Dressings should be changed regularly and as soon as they become soiled with urine or feces to prevent wound contamination. Each dressing change should be accompanied by concurrent wound reassessment.

Algorithm for help in choosing an appropriate class of dressings for pressure ulcer management. *Gauze dressings can be used if limited options available require more frequent dressing changes.

Dressings available for pressure ulcer management with advantages, disadvantages, and ideal use

Gauze dressings

The traditional wet-to-dry method of gauze dressing now has more limited use in the treatment of pressure ulcers. While the materials are inexpensive, they do require frequent changes and the related nursing expense needs to be factored in when determining their true cost. 44 When properly performed, they help maintain a moist wound environment, and the gauze also serves the role of performing a superficial debridement of biofilm and small amounts of necrotic tissue during dressing changes due to its adherent nature. 45 The advent of advanced dressing materials makes gauze dressings a fallback when nothing else is readily available. 46 Dry gauze dressings should not be used to treat pressure ulcers.

Alginate dressings

Alginate is a very absorbent material that is ideal for use in wounds with moderate to high discharge. They can absorb several times their weight in exudate and can conform well to irregular or tunneled wounds. Alginate dressings can be used in the setting of infected wounds and can be left in place longer than most dressings. 47

Foam dressings

Foam dressings are made from polyurethane, a semipermeable material that can accommodate a medium to high amount of wound exudate and can be used in infected pressure ulcers. Foam dressings are often used for prevention of pressure ulcers because they provide some cushion. Silicone is often used in combination with foam dressings (such as Allevyn, Mepilex, and Optifoam) and is helpful in the setting of fragile tissue surrounding pressure ulcers. Dressings with silicone are less likely to cause trauma to skin on removal compared to other adherent dressings. 48

Hydrocolloid dressings

Hydrocolloid dressings are made of a foam or film polyurethane material and contain a gelatin- or sodium carboxymethylcellulose-based gel material, which gives it the ability to absorb some fluids. They are well suited for wounds that have minimal to moderate drainage and are often used on Stage II and Stage III pressure ulcers. 46

Hydrogel dressings

Hydrogel dressings are gel based and are 90% water. These dressings are therefore ideally used in dry or dehydrated wounds and are often used over granulation tissue. In addition to being available in sheet form (where hydrogel is placed over a thin fiber mesh) and in the form of impregnated gauze, hydrogel also comes in its pure form in tubes and can be placed at the base of an uninfected granulating wound. This dressing should be covered by a sturdier dressing to prevent dislocation and dehydration of the hydrogel. 49

Silver-containing dressings

Silver has bactericidal properties and dressings that are impregnated with silver are ideal for use in infected wounds. This dressing should be discontinued after clearance of infection as it can delay wound healing due to its toxicity to keratinocytes and fibroblasts. Silver is often incorporated into foam and alginate dressings. Silver alginate comes in rope and square forms, which are well suited for infected wounds with exudate, and gel form, which is better suited for drier wounds. 50

Honey-containing dressings

There are anecdotal reports of the use of honey in the treatment of wounds since antiquity. In modern times, there is currently low evidence for the use of honey in the setting of pressure ulcers. 28 Medical-grade honey has been shown to have mild antibiotic properties. Medical honey comes in stand-alone forms of gel or paste as well as impregnated into dressings where it is combined with alginate or hydrocolloid materials.

Transparent film dressings

Transparent film dressings are used primarily to protect Stage I or II ulcers where the skin remains intact. They provide a barrier to urine, stool, and other bodily fluids, which can macerate the skin. Because they are transparent and allow for observation of the wound, they can be applied and left in place for days. These dressings should not be applied in any ulcer where there is exudate as they are not porous. Care must be taken to remove these dressings as they can rip skin if removed forcefully. 51

Negative pressure wound therapy

Negative pressure wound therapy (NPWT) consists of a foam dressing, which can be tailored to fit the patient's wound and is covered by a transparent film to enable creation of a vacuum in the wound when the foam is attached to a suction device via tubing. NPWT has been shown to speed wound healing in chronic wounds and the prevailing theory is that the vacuum causes the cells in the wound bed to sense a mechanical force. 52 Mechanical forces stimulate the proliferation of fibroblasts leading to improved healing. The presence of the vacuum continuously eliminates exudate making it ideal in wounds where there is heavy exudate. Before application of the NPWT device, the wound must be adequately debrided. The foam dressing is easy to conform to wounds with unusual shapes, tunneling, and undermining. Because of the transparent film required for the vacuum to hold, NPWT is useful for preventing additional wound contamination. Randomized controlled trials showed no advantage of NPWT over other dressings. 53 As with any dressing, its use is dictated by its properties. Wounds with a heavy exudate are readily managed with NPWT. It has been found to be helpful in wounds adjacent to fecal flow where its seal prevents wound contamination. Contraindications to NPWT use include uncorrected coagulopathy, exposed vital organs or large vessels. 53 A nonadherent dressing can be placed below the foam to decrease pain on removal of foam dressing and during suctioning over the wound bed.

Other therapies

Biophysical treatments, including direct electric stimulation, pulsed electromagnetic field, and pulsed radio frequency energy, have been used to promote wound healing. Phototherapy treatment of pressure ulcers has been performed using laser, infrared, and ultraviolet waves. Studies have shown equivocal evidence concerning laser and infrared treatments, but ultraviolet C light therapy has been shown to decrease the bacterial burden and can be used following wound debridement in persistently infected wounds. 54 Hyperbaric oxygen therapy and topical oxygen therapy have been used for pressure ulcer treatment with equivocal results. 55

Biologic dressings describe a group of products derived from skin structures that have been purported to speed healing. They can be derived from nonhuman and human sources and are applied to noninfected, well-granulated wounds. The products range from decellularized human and porcine skin to dressings containing human fibroblasts and keratinocytes. Collagen is the main connective tissue fiber and application of collagen to uninfected granulating wound base can theoretically stimulate wound healing by providing a matrix network for cells to migrate into. These biologic dressings are typically used when an ulcer has fully granulated in, but still has a significant area of un-epithelialized wound. The dressings can be used in lieu of skin grafting to prevent having a second wound that needs attention. Growth factors have also been used by themselves to increase wound healing by stimulating angiogenesis and matrix deposition. 56

Patient optimization

In addition to treatment of the pressure ulcer itself, it is important to treat the overall patient as well. Physical measures to relieve pressure have already been described. Hyperglycemia will retard wound healing and diabetics should be aggressively treated to maintain glycemic control. The immune system has been shown to have a vital role in wound healing and immunosuppression will slow healing. Attention should be directed to any therapy that can cause immunosuppression, and these medications should be optimized to provide appropriate therapy without excessive immunosuppression. Proper wound healing requires adequate blood supply. For any pressure ulcer in the extremities, perfusion should be assessed and vascular surgery consulted if it is determined to be inadequate to support proper healing. 5 , 7 Finally, we will stress once again the need to provide adequate nutrition. Periodic assessments of adequate nutrition should be performed by checking serum markers of nutrition such as albumin and prealbumin. Dietary intake should be adjusted to ensure the patient is in positive nitrogen balance. 27

Control of contamination

By default, any open pressure ulcer is superficially contaminated with environmental flora. However, it is important to prevent added contamination if the wound is near the fecal stream as in ischial or sacral pressure ulcers. An added concern is that stool and urine can be irritating to the skin, causing further skin breakdown and extension of the ulcer. Because a large number of patients with pressure ulcers are incontinent of both bowel and bladder, it is important to consider how to deal with this. At the very least, these patients require frequent changes of their diapers to minimize skin contact with urine and stool. Consideration should be given to placement of a urinary catheter with the understanding that discomfort and complications, including urinary tract infection, are possible. Rectal tubes can be used but are rarely useful due to solid stools. 57

Diversion of the fecal stream through surgical placement of a colostomy can be undertaken in those cases where it is felt to be necessary to allow proper healing. Any discussion of fecal diversion should include consideration of the likelihood that the colostomy will be permanent. Many of the patients who develop severe sacral and ischial pressure ulcers are incontinent or require a bowel program due to underlying conditions such as dementia or spinal cord injury. In these patients, having a permanent colostomy can actually be beneficial in their long-term care. 58

Surgery for reconstruction

Although the majority of pressure ulcers will heal following debridement and conservative treatments outlined above, sometimes surgery will allow more rapid resolution of the ulcer. It should be noted that patients with poorly healing wounds should first be assessed for why the wound is not closing as those same factors could risk failure of surgical reconstruction. There are a variety of techniques available ranging from a simple skin graft to pedicled or, rarely, microvascular flaps for coverage. The appropriate candidate for surgical reconstruction has a wound that is without purulence, well-granulated and well-protected from soilage. The patient should be adequately nourished as assessed by nitrogen balance, albumin, and prealbumin, and without acute medical problems separate from the wound. Any intrinsic problems that can delay healing should be optimized, that is, well-controlled blood sugars in diabetics. In the appropriate patient, reconstruction will speed healing. Composite local tissue flaps are most frequently used to provide adequate tissue protection and perfusion. There are innumerable approaches to tissue coverage and the plan for each patient needs to be individualized. The flaps are planned so that suture lines remain away from pressure sites to ensure the best chance for healing. 59 Microvascular tissue transfer is rarely used but indicated when local options for creating a flap are exhausted. 60 Careful surgical planning is required to assure options for future reconstructions in cases of flap failure or pressure ulcer recurrence.

Among the indications for using surgical reconstruction are very large wounds, wounds with exposed organs and vessels, chronically nonhealing wounds, and wounds with osteomyelitis. Chronically infected bone will not allow appropriate healing of the overlying tissue. Prolonged antibiotics are often inadequate in curing the infection. A surgical approach to healing the ulcer requires debridement of the infected bone and placement of a well-vascularized flap to cover the area can allow the infection to be cured.

Pressure ulcer prevention remains the most important step in the management of these wounds. However, despite best efforts, pressure ulcers may develop if enough risk factors are present. Treatment of pressure ulcers is necessary for patient comfort and to decrease risk of systemic infection. The mainstays of treatment as outlined above include debridement of devitalized tissue, control of remaining infection with antibiotics, medical and nutritional patient optimization, appropriate dressing selection, and frequent monitoring of progression of wound evolution. If standard approaches are not adequate, additional therapies can be pursued, including biophysical modalities. Finally, in large ulcers, ulcers where wound healing is not adequately progressing, or ulcers where chronic osteomyelitis is present, reconstructive surgery can be considered.

Take-Home Messages

• • Pressure ulcers represent a large and growing biomedical burden to society.
• • Understanding prevention and treatment is necessary for wound care specialists.
• • Novel dressings and therapies have not shown increased benefit over others, but they have utility based on specific patients.
• • A major target for research should be improved prevention, given penalties now in place of hospital-acquired pressure ulcers.

Abbreviations and Acronyms

Acknowledgment and Funding Sources

The authors acknowledge generous support from the Hagey Laboratory for Pediatric Regenerative Medicine.

Author Disclosure and Ghostwriting

No competing financial interests exist. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article.

About the Authors

Tatiana V. Boyko, MD, is a general surgery resident at the University at Buffalo currently performing a postdoctoral research fellowship at Stanford University. Michael T. Longaker, MD, MBA, is the Deane P. and Louise Mitchell Professor of Surgery at Stanford University School of Medicine. He is the Director of the Hagey Laboratory for Pediatric Regenerative Medicine and the Co-Director of the Institute of Stem Cell Biology and Regenerative Medicine. George P. Yang, MD, PhD, is an Associate Professor of Surgery at Stanford University School of Medicine.