Risk Factors, Management and Other Correlates of Peptic Ulcer Disease in a University Community in South-South Nigeria
Eniojukan JF1*, Okonkwo OC2 and Adje UD2
1Department of Clinical Pharmacy and Pharmacy Practice, Niger Delta University, PMB 071, Wilberforce Island, Bayelsa State, Nigeria
2Department of Clinical Pharmacy and Pharmacy Administration, Delta State University, PMB 1, Abraka, Delta State, Nigeria
Received: 01-Dec-2017 , Accepted: 20-Dec-2017
Keywords: Peptic Ulcer Disease, Prevalence, Patterns, Management, Nigeria
How To Cite
The most common causes of peptic ulcer disease (PUD) are Helicobacter pylori infection and use of non-steroidal anti-inflammatory drugs (NSAIDs).Treatment choices include standard triple therapy. This study evaluated the patterns of prevalence, life-style risk factors and correlates of management of PUD among Staff and Students of Delta State University, Abraka Campus, Nigeria. A descriptive cross sectional study was initiated among 450 willing staff and student respondents. A total of 126 respondents that had been diagnosed for PUD were further evaluated for prevalence and patterns, confounding life-style factors, drug therapy and other correlates of PUD management by using self-designed, pre-tested questionnaires that addressed the objectives of the study. Data was analyzed using Statistical Package for Social Sciences, version16.0 (SPSS Inc. Chicago Illinois). Duodenal Ulcer (DU) had a higher prevalence than Gastric Ulcer (GU) in a ratio of 1.5:1. The prevalence of GU was higher among Staff, Males and those older than 35 years; DU had a higher prevalence among the Students, Females and 16-35 yrs age group. The greatest life-style risk factors identified were consumption of NSAIDs, Tobacco and Alcohol. Regarding drug treatment, over 90% of drugs prescribed were antibiotics; nearly all respondents claimed to experience side-effects which included Diarrhea, Abdominal Pain and Headache; nearly all respondents often adhered to instructions to avoid Alcohol. In this population, PUD prevalence and pattern was structured along gender and age. There were issues with life-styles which could have contributed to the pathophysiology of PUD. Patients experienced some side-effects that affected adherence to instructions. Management seemed appropriate with the use of triple therapies. However, there is still a dire need for strategic health education on PUD risk factors and self-care practices.
Excessive acid production was presumed to be responsible for inducing ulcer disease, and this premise informed the focus of management on the use of drugs that neutralize and/or inhibit the secretion of stomach acid. Even though the acid theory is still considered valid, the preponderant cause of ulcer disease is now believed to be infection of the stomach by a bacterium called "Helicobacter pyloridus" (H. pylori); it is claimed to be responsible for about 70-90% of ulcer cases1, 2.In Nigeria, almost 100% of duodenal ulcer and 82% of gastric ulcer patients are H. pylori positive3.Based on the H. pylori theory, the institution of treatment protocols such as “triple therapy,” has been instituted. Triple therapy is the use of a proton-pump inhibitor (PPI) or H2 blocker which reduces gastric acid secretion, with either two different antibiotics or an antibiotic combined with bismuth salicylate. Other treatment choices include sequential therapy, quadruple therapy, and levofloxacin-based triple therapy4
Many other risk factors for PUD have been identified in literature. These include, among many others, the use of anticoagulants, corticosteroids, smoking, coffee and stress5,6. The long-term use of NSAIDs especially in the presence of H. pylori infection has been linked with greater risk of PUD. The prophylactic use of misoprostol and proton pump inhibitors has been recommended for such patients4.
This study was carried out to identify patterns of PUD, the confounding factors and correlates of its management among Staff and Students of Delta State University, Abraka Campus, South of Nigeria.
2.1 Study population
The study was carried out among staff and students of the three campuses that make up the Abraka Campus of Delta State University with an estimated population of less than 10,000.
2.2 Study design and sample
A descriptive cross sectional study was initiated among 450 willing staff and students in the various Faculties and Departments that constituted the Delta State University, Abraka Campus.
A total of 126 respondents that had been diagnosed for PUD were further evaluated for patterns of PUD, drug therapy and other correlates of PUD management, which included risk factors, types of therapy, side-effects experienced, self-reported effectiveness of therapies and self-care practices.
The sample size was calculated using the Cochran formula7. A purposive and convenient sampling technique was adopted for the study; 150 questionnaires were allocated to each of the three campuses; respondents were visited in their offices (staff) and class rooms (students).
2.3 Data collection
A self-designed, pre-tested questionnaire that addressed the objectives of the study was used. The questionnaires were designed to retrieve demographic information, patterns of prevalence of PUD, prevalent risk factors, PUD management, drug procurement practices, counseling practices, Side effects and compliance to instructions. A panel of 3 experts (2 professors of pharmacy and a consultant statistician) determined the questionnaire content validity.
2.4 Data analysis
Data was analyzed using Statistical Package for Social Sciences, version16.0 (SPSS Inc. Chicago Illinois). Results were presented as means ± standard deviation for quantitative variables and number (percentages) for qualitative variables. Categorical variables were compared with
Pearson’s Chi-square. Significant P-value was taken as <0.05.
2.5 Ethical considerations
Permissions were taken from Delta State University management. Privacy of all interviews was ensured and prior informed consents of respondents were taken after explaining the purpose and benefits of the study.
3.1 Demographic profile of PUD patients
A total of 126 respondents participated in the study and response rate was 100%.
Over 70% of the respondents were aged between 16 and 25 years; 60% were females; 78% were Christians; 76% were students; 70% were not married. About 70% were undergraduates.
3.2 Patterns of prevalence of PUD among respondents
The prevalence of GU and DU was 40% and 60% respectively. The prevalence of GUand DU among the males was 40% and 30% respectively; and among the females, 13% and 17% respectively for GU and DU. The prevalence of GU and DU in Staff was 42% and 15% respectively; the prevalence of GU and DU in Students was 10% and 33% respectively.
GU and DU prevalence among the 16-35 year-olds was 6% and 21% respectively; GU and DU prevalence among respondents older than 35 years was 56% and 17% respectively (Table 1).
3.3 Risk factor assessment
A total of 68%, 60%, 56%, 48%, 47%, 44% and 41% respectively consumed tea/coffee, anti-malaria drugs, fruit juices, carbonated, alcohol, paracetamol and tobacco. About a third of respondents took milk drinks, multivitamins, energy drinks and herbal medicines. About a fifth of respondents took beer, antibiotics and Tramadol; about a tenth of respondents took indomethacin, diclofenac, ibuprofen and the local gin (Table 2).
3.4 Management and drug procurement patterns
In terms of recommended therapies, 93%, 86% and 79% respectively were placed on Antibiotics, PPIs and Antacids. Combination therapies largely involved PPI +Antacid + Antibiotic (48%) and PPI + Sucralfate + Antibiotic (29%); 14% were using PPI + Antacid + Antibiotic + Herbal.
In terms of drug procurement sources, majority (87%) utilized Hospitals and Community Pharmacies; only 1% patronized Open Markets, Hawkers and Supermarkets.
Regarding Additional therapies, nearly all respondents (93%) took analgesics; 64% took Anti-emetics.
On self-reported effectiveness of therapy, 71% of respondents rated their therapy as High; 7% rated it as not effective. See Table 3.
3.5 Counseling practices
All respondents were placed on special diet; majority were counseled to avoid Milk (93%), Alcohol (86%), Spicy Foods (79%) and Chocolate/Coffee (71%)(Table 4).
3.6 Side effects and compliance correlations
Majority (95%) of claimed to experience some form of Side-effects; frequencies of such side-effects include Diarrhea (67%), Abdominal Pain (49%) and Headache (25%). Majority (43%) of claimed the side-effects sometimes affected how regularly they took their drugs.
Regarding adherence to specific instructions, 48%, 63% and 91% respectively often adhered to instructions to avoid Aspirin, Spicy foods and Alcohol; 76% of respondents always adhered to instructions to avoid smoking. (Table 5).
4.1 Demographic data of respondents
Among the initial total respondents,a total of 126 respondents out of 450 were identified as PUD patients making a PUD prevalence of 28%.Majority were females, undergraduates, Christians and single.
4.2 Patterns of prevalence of PUD among respondents
In this study, DU had a higher prevalence than GU in a ratio of 1.5:1. This closely tallies with two studies that reported the ratios of 1.55:18 and 1.2:19 but slightly lower than 3.8:1 as reported by other researchers10. Thus, globally, it would appear that the trend of prevalence is higher for DU. It is reported that both DU and GU differ in their pathogenesis, clinical presentation and management strategies11.
The prevalence of GU was higher than DU among Staff respondents; the ratio of GU to DU in this population was 2.8: 1. This is not coming as a surprise as we expect to have more elderly respondents among this population. Conversely, this study revealed a higher prevalence of DU among the Students (DU to GU ratio of 3.3: 1) of lower age-group. This further supports the claim of higher prevalence of GU among the elderly12. Indeed, a study reported that DU is ten times more common than GU in young patients13.
Regarding gender differentials, this study showed that GU was more prevalent in males than DU (GU to DU ratio of 1.3: 1). Conversely, DU was more prevalent among the females (DU to GU ratio of 1.3:1). In essence, this study showed that GU had a higher prevalence among the Males whereas DU had a higher prevalence among the Females. Males are supposedly involved in greater and more vigorous physical activities and may be predisposed to consuming NSAIDs as pain relievers than their female counterparts. Hence, there is the tendency for males to develop more of GU than the females. Alternatively, the population may consist of older males.
Regarding Age, there was a higher prevalence of DU among respondents in the 16 -35 yrs age group (Ratio of DU to GU was 3.5: 1). Conversely, there was a higher prevalence of GU among respondents older than 35 years (GU to DU ratio was 3.3: 1). These data support the literature that GU is more prevalent among the elderly12,13.
4.3 Risk factor assessment
In this population, the greatest risk factors identified were consumption of NSAIDs, Tobacco and Alcohol.
Tobacco, Alcohol and NSAIDS are known risk factors for the development and maintenance of PUD in general,4, 14,15.
The literature identified other risk factors to include anticoagulants, corticosteroids, diet (Spicy Food), H. Pylori, stress, past history of PUD, genetics and gender. Further, excess acid production from tumors of the acid producing cells of the stomach (gastrinomas) has been identified as a cause of PUD.
Smoking is considered a risk factor because it is said to elevate the risk of ulcers and impairs the healing process. Alcohol consumption is said to cause similar effects16.
In this study, more than two-third of respondents took Tea/Coffee. These contain Caffeine and other products, which can make it difficult to differentiate effects of caffeine per se from other compounds17,18.
Further, about a third of the respondents took energy drinks which are thought to contain 70-120 mg Caffeine per 330 ml18.
Most studies have focused on Coffee and not Caffeine per se. The position is canvassed that there is no apparent link between gastro-intestinal disorders / complaints and consumption of coffee19,20.
In this study also, about a third of the respondents took milk drinks.The role of milk in the pathogenesis and prognosis of PUD has long been controversial. Most studies indicate that milk may reduce the pains of DU, has no beneficial effects on ulcer healing process and may actually increase acid production and also reduce the healing rate21,22.
Milk products like Yoghourt, fermented and unfermented milk are thought to be loaded with probiotics that encourage healthy digestion and soothe irritated ulcers by replacing harmful bacteria in the gastrointestinal tract with healthy bacteria23.
About half of respondents consumed carbonated drinks and fruit juices. These substances often contain high amounts of citric acid, a known risk factor for hyperacidity and indigestion. These and similar products like lime, lemon, pineapple, jam and jellies are, therefore, better avoided especially by PUD patients24
About a third of respondents took herbal medicines. Most herbal formulations are very rich in anti-oxidants and have antimicrobial, anti-inflammatory, anti-rheumatic and anticancer activities in addition to their gastro-protective and anti-ulcer activities25,26. These effects may underlie the beneficial effects users experience.
4.4 Management and drug procurement patterns
Over past several years, the major cause of PUD was assumed to be excessive acid production, which informed the use of agents that neutralized and / or inhibited acid secretion in the stomach. This concept has since changed following the identification of H. pylori as a primary cause of PUD in the majority of patients (70 – 90%). Numerous gastro-intestinal disorders have been linked to HP infection worldwide27,28. Notable among these is its major pathophysiologic role in gastric cancer29,30. Thus, HP eradication has since become the main thrust in the management of peptic ulcer disease and other gastro-duodenal disorders,31,32.Studies have since shown that HP eradication leads to reduction in the severity of gastritis and PUD recurrence rate33,34.In the last decades, the standard 3-drug regimen (amoxicillin, clarithromycin, and metronidazole)has been widely used in many countries as a first step regimen for the purpose of eradicating HP32,35,36.The recommended first-line treatment for HP is the combination of a PPI with two antimicrobial agents – clarithromycin and amoxycillin or metronidazole; often referred to as the standard triple therapy37.
In this study, over 90% of drugs prescribed were antibiotics. This is in recognition of the cardinal strategy to eradicate H Pylori. Further, over 80% and 79% of drugs prescribed were PPIs and Antacids, respectively. Only about a third of prescribed drugs were Sucralfate. The latter is an effective alternative to Antacids in PUD management.
In this study, the preponderant combination therapy utilized was PPI + Antacid + Antibiotic. This conforms to the focus and objectives of PUD management. About a third of combination therapies involved PPI + Sucralfate + Antibiotics.
In this study, about a tenth of combination therapies involved 2 drug combinations of Antacids + Antibiotics.
Further, in this study, a little over one-tenth of respondents used Herbal Medicines in addition to PPI, Antacid and Antibiotics.
Spices and herbal remedies have been used since ancient times to treat a variety of disorders. It has been experimentally demonstrated that spices, herbs, and their extracts possess antimicrobial, anti-inflammatory, antirheumatic, lipid-lowering, hepatoprotective, nephroprotective, antimutagenic and anticancer activities, besides their gastroprotective, anti-ulcer activities. They have been demonstrated to have anti- Helicobacter pylori effects and mechanisms regulated by nitric oxide, prostaglandins, non-protein sulfhydryl molecules and epidermal growth factor expression. Accordingly, their consumption may, therefore attenuate and help prevent peptic ulcer disease25,26.
Regarding additional therapies, Analgesics and Anti-emetics were more commonly used.
Epigastric pain, Nausea and vomiting are common symptoms of PUD and may have been responsible for the use of these drugs.
Regarding self-reported effectiveness of therapies, over 70% of respondents rated their therapies as high; less than one-tenth rated their therapies as in-effective.
The high level of effectiveness reported in this study is in conformity with the appropriateness of the combination therapies used in the management of their PUD.
In terms of drug procurement practices, a large majority of respondents sourced their drug products from the most appropriate sources of quality products -Hospital and Community Pharmacies; only a mere 1% of them patronized open markets, hawkers and supermarkets. This is highly commendable.
4.5 Counseling practices
There are self-care practices that PUD patients should be aware of and engage in order to adequately promote the ulcer healing process. These include adequate adherence to prescribed medications, appropriate self-medication and avoidance of aggravating risk factors like smoking, alcohol, and dietary restrictions where necessary38,39.
In this study, over 70% of respondents were counseled to avoid milk, spicy foods, alcohol and Chocolate/Coffee. All respondents were placed under some form of special diet.
It is generally recommended that the consumption of healthy diet is of immense advantage to the intestinal tract and one’s health in general. To this end, eating a diet rich in fruits, vegetables and fiber is recommended40,41.
Generally, since the introduction of H2-inhibitors, it has become unnecessary to introduce special diets for patients with peptic ulcer. The dietary focus should be the avoidance of unnecessary upsurges of gastric acid secretion and direct gastric mucosa irritation42.
Generally, PUD patients should eat a healthy balanced diet. It really serves no purpose to eat more often or increase the amount of milk and dairy products taken; it may be counter-productive. PUD patients are commonly advised to:
- Avoid foods and drinks that cause discomfort like alcohol, coffee, caffeinated soda, fatty foods, chocolate, and spicy foods.
- Avoid spicy foods, such as chilies, hot peppers and hot sauce as they can increase stomach acid, trigger acid reflux and worsen symptoms associated with stomach ulcers.
- Avoid eating late night snacks.
- Quit Tobacco as it slows the healing process and increases recurrence
- Reduce stress level and learn ways to better manage stress.
- Avoid NSAID such as aspirin, ibuprofen, or naproxen. If, required, to take Paracetamol to relieve pain.
- Take all medicines with plenty of water22,43,44.
4.6 Side effects and compliance correlations
In this study, nearly all respondents claimed to experience side-effects, which included diarrhea, abdominal pain and headache.
These are well-known side-effects and did not come as a surprise. Individual tolerance levels may, however, differ.
Important to note that a significant number (43%) of respondents claimed that the side-effects they experienced sometimes affected how regularly they took their drugs. This situation is quite worrisome as it may result into delayed ulcer healing consequent upon inadequate adherence and, possibly, early emergence of resistance. Appropriate therapeutic counseling is needed for such patients. Alternative drugs may be required.
Regarding adherence to specific instructions, this study revealed variable responses. Whereas, nearly all respondents often adhered to instructions to avoid alcohol, only about half often adhered to instructions to avoid aspirin; majority (63%) often abided by instructions to avoid spicy foods. Significantly, majority (76%) of respondents always adhered to instructions to avoid Smoking.
Total adherence to avoidance of aggravating factors is needed to promote ulcer healing and / or prevention of worsening of the condition.
In this study, DU had a higher prevalence than GU in a ratio of 1.5:1. The ratio of DU to GU differs with status, gender and age. In this population, the greatest risk factors identified were consumption of NSAIDs, tobacco and alcohol. The preponderant combination therapy utilized was PPI + Antacid + Antibiotic. Majority of respondents rated their therapies as high effective.
Majority were counseled to avoid milk, spicy foods, alcohol and chocolate/coffee. All respondents were placed on some form of special diet; nearly all respondents claimed to experience side-effects which sometimes affected how regularly they took their drugs; nearly all respondents often adhered to instructions to avoid alcohol, and majority always adhered to instructions to avoid smoking.
There is need for strategic health education on PUD risk factors and self-care practices.
We acknowledge the cooperation of all respondents which resulted into the success of this study.
7 Conflict of interest
8 Authors’ contribution
EJF: Concept, Data analysis, Manuscript review, Final draft manuscript
AUD: Concept, Data Analysis, Manuscript review
OOC: Data collection, Data analysis, Draft manuscript
- Mégraud F. A humble bacterium sweeps this year`s Nobel Prize. Cell.2005;123:975–6.
- Fischbach W, Malfertheiner P, Hoffmann JC, Bolten W, Kist M, Koletzko S. Helicobacter pylori and gastroduodenal ulcer disease.Dtsch. Arztebl. Intl.2009: 106(49): 801-808.
- Ndububa DA, Agbakwuru AE, Adebayo RA, Olasode BJ, Olaomi OO, Adeosun OA, Arigbabu AO. Upper gastrointestinal findings and incidence of H. pylori infection among Nigerian patients with dyspepsia. West Afr. J. Med. 2001; 20(2): 140-145.
- Fashner J,Gitu AC. Diagnosis and Treatment of Peptic Ulcer Disease and H. pylori Infection. Am Fam Physician.2015;91(4):236-242.
- Lanza FL, Chan FK, Quigley EM. Guidelines for prevention of NSAID-related ulcer complications. ; Practice Parameters Committee of the American College of Gastroenterology. Am J Gastroenterol. 2009; 104(3):728-38.
- Bashinskaya B, Nahed BV, Redjal N, Kahle KT, Walcott BP. Trends in Peptic Ulcer Disease and the Identification of Helicobacter Pylori as a Causative Organism: Population-based Estimates from the US Nationwide Inpatient Sample. Journal of Global Infectious Diseases.2011:3(4), 366–370.
- Cochran WG. Sampling techniques. 1977; (3rd ed.). New York: John Wiley & Sons.
- Tijjani B, Umar A. Peptic ulcer disease and helicobacter pylori infection at Kano, Nigeria.. The Internet Journal of Gastroenterology. 2008; 8(1).
- Wang, AY; Peura, DA. “The prevalence and incidence of Helicobacter pylori-associated peptic ulcer disease and upper gastrointestinal bleeding throughout the world”. Gastrointestinal endoscopy clinics of North America.October 2011: 21 (4): 613–35.
- Rosenstock SJ, J0rgensen T. Prevalence and incidence ofpeptic ulcer disease in a Danish County a prospective cohort study. Gut 1995; 36: 819-824.
- Kasper D, Braunwald E, Fauci A, Hauser A, Longo D, Jameson L. Harrison`s Manual of Medicine, 16th ed., 2004; p. 729, McGraw- Hill, New York.
- WebMd. Understanding Ulcers. 2017. http://www.webmd.com/digestive disorders/understanding-ulcers-basic-information.
- Gerald M and Lawrence W. Current Surgical diagnosis and treatment, 12th ed. 2006; PP: 513-515, Raw-Hill Companies, New York.
- Tovey FI, Bardhan KD, Hobsley M. Dietary phosphilipids and sterols protective against peptic ulceration. Phytother Res.2013; 27(9):1265-9.
- Siddique Rafi AH. Prevalence of Peptic Ulcer Disease among the Patients with Abdominal Pain Attending the Department Of Medicine in Dhaka Medical College Hospital, Bangladesh . IOSR Journal of Dental and Medical Sciences.2014;13(1),Ver. IX: 05-20.
- WebMd. Digestive Disorders Health Center, September 2012.
- Harland BF. Caffeine and nutrition. Nutrition. 2000:7(8): 522-526.
- Heckman MA, Weil J, Gonzalez de Mejia E. Caffeine (1, 3, 7-trimethylxanthine) in foods: a comprehensive review on consumption, functionality, safety, and regulatory matters. J Food Sci, 2010:75: R77-87.
- Shimamoto T, Nobutake Y, Shinya K, Yu T, Mitsuhiro F, Masashi O et al. No Association of Coffee Consumption with Gastric Ulcer, Duodenal Ulcer, Reflux Esophagitis, and Non-Erosive Reflux Disease: A Cross-sectional study of 8,013 Healthy Subjects in Japan. PLoS One,2013: 8(6); e65996.
- Rubach M, Lang R, Seebach E, Somoza MM, Hofmann T, Somoza V. Multi-parametric approach to identify coffee components that regulate mechanisms of gastric acid secretion. MolNutr Food Res.2011: 56(2): 325-35.
- Briffa J .Why milk isn`t the answer for stomach ulcers. Daily Mail. 2017.
- MedlinePlus. Peptic Ulcer Disease – Discharge. 2017. https://medlineplus.gov/ency/patientinstructions/000380.htm accessed 13/09/2017.
- Tirtha, SSS. The Ayurveda Encyclopedia: Natural Secrets to Healing, Prevention, and Longevity Paperback. Ayurveda Holistic Center Press; 2nd Revised edition. 2007.
- Bethany Fong RD. Foods to Avoid When You Have a Stomach Ulcer.2017.
- Bengmark S. Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases. JPEN J Parenter Enteral Nutr. 2006; 30: 45-51.
- Al Mofleh IA. Spices, herbal xenobiotics and the stomach: Friends or foes? World J Gastroenterol.2010; 16(22): 2710-2719.
- Sezer S, IbiÅŸ A, Ozdemir BH, Ozdemir FN,Külah E, BoyacioÄŸlu S, et al. Association of Helicobacter pylori infection with nutritional status in hemodialysis patients. Transplant Proc. 2004; 36: 47-49.
- Aydemir S, Boyacioglu S, Gur G, Demirbilek M, Can FK, Korkmaz M, et al. Helicobacter pylori infection in hemodialysis patients: susceptibility to amoxicillin and clarithromycin. World J Gastroenterol.2005;11: 842-45.
- Bytzer P, Dahlerup JF, Eriksen JR, Jarbøl DE, Rosenstock S, Wildt S. Diagnosis and treatment of Helicobacter pylori infection. Dan Med Bull. 2011; 58: C4271 .
- Ergül B, KoçakE, TaÅŸ A, Filik L, Köklü S. Bismuth, moxifloxacin, tetracycline, lansoprazole quadruple first line therapy for eradication of H. pylori: A prospective study. Clin Res HepatolGastroenterol. 2013;37: 527-529.
- Walsh JH and Peterson WL. The treatment of Helicobacter pylori infection in the management of peptic ulcer disease. N Engl J Med.1995; 333: 984-91.
- Take S, Mizuno M, Ishiki K, NagaharaY, Yoshida T, Yokota K, et al. The effect of eradicating Helicobacter pylori on the development of gastric cancer in patients with peptic ulcer disease. Am J Gastroenterol.2005; 100: 1037-42.
- Kashiwagi H. Ulcers and gastritis. Endoscopy. 2003; 35: 9.
- Sun WH, Ou XL, Cao DZ, Yu Q, Yu T, Hu JM, et al. Efficacy of omeprazole and amoxicillin with either clarithromycin or metronidazole on eradication of Helicobacter pylori in Chinese peptic ulcer patients. World J Gastroenterol. 2005; 11: 2477-81.
- Ma J, Liu W, Zhang L, Pan K, Zhao H, Zhou T, et al. A placebo-controlled trial of 10-day bismuth-based quadruple therapy to eradicate Helicobacter pylori infection; a pilot study for the large Linqu County trial. Eur J Gastroenterol Hepatol.2010; 22: 597-601.
- Sasaki M, Ogasawara N, Utsumi K, Kawamura N, Kamiya T, Kataoka H, et al. Changes in 12-year first- line eradication rate of Helicobacter pylori based on triple therapy with proton pump inhibitor, amoxicillin and clarithromycin. J ClinBiochemNutr. 2010; 47: 53- 58.
- Cho DK, Park SY, Kee WJ, Lee JH, Ki HS, Yoon KW, et al. The trend of eradication rate of Helicobacter pylori infection and clinical factors that affect the eradication of first-line therapy].Korean J Gastroenterol. 2010; 55: 368-375.
- Li LF, Chan RLY, Lu L, Shen J, Zhang L, Wu WKKet al. Cigarette smoking and gastrointestinal diseases: The causal relationship and underlying molecular mechanisms (Review). International Journal of Molecular Medicine. 2014; 34(2): 372-380.
- Owonaro PA, Eniojukan JF, Owonaro AED. Smoking Pattern, Reasons, Effects and Other Correlates of Smoking in Yenagoa Council Area of Bayelsa State. Ortho & Rheum Open Access. 2017; 4(5): 555649.
- Andrew HS. Peptic ulcer disease: Genetic, environmental, and psychological risk factors and pathogenesis. 2011.
- Johnson S. Stomach Ulcers and What You Can Do About Them. 2017.
- Marotta RB, Floch MH. Diet and nutrition in ulcer disease. Med Clin North Am. 1991;75(4):967-79.
- Chan FKL, Lau JYW. Peptic ulcer disease. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran`s Gastrointestinal and Liver Disease. 10th ed. Philadelphia, PA: Elsevier Saunders: 2016.chap 53.
- Kuipers EJ, Blaser MJ. Acid peptic disease. In: Goldman L, Schafer AI, eds. Goldman-Cecil Medicine.25th ed. Philadelphia, PA: Elsevier Saunders: 2016; chap 139.