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Laser photocoagulation for the treatment of acute peptic-ulcer bleeding. A randomized controlled clinical trial.

We tested the hypothesis that therapeutic endoscopy using the Nd:YAG (neodymium:yttrium-aluminum-garnet) laser would benefit patients with acute peptic-ulcer bleeding. Over 43 months, 174 patients with active bleeding (n = 32) or stigmata of recent bleeding (n = 142) due to peptic ulcers were randomly assigned during endoscopy to either standard treatment with laser photocoagulation or therapy without photocoagulation. There were no significant differences in a number of outcomes between the group treated with laser photocoagulation and the control group. Continued bleeding or rebleeding was observed in 22 percent of the laser-treated group and in 20 percent of the control group. Urgent surgery was necessary in 16 percent of the laser-treated patients and in 17 percent of the controls. Laser-treated patients spent a mean of 41 hours in the intensive care unit, and controls spent a mean of 32 hours. The mean hospital stay was 12 days in the laser-treated group and 11 days in the control group. One death occurred in each group. When patients with active bleeding were analyzed separately, there was no significant difference in outcome, even though laser photocoagulation stopped active bleeding in 88 percent of cases. Among patients with visible vessels, rebleeding occurred in 5 of 14 (36 percent) who received laser treatment and 2 of 15 (13 percent) who did not. Laser treatment precipitated bleeding in four patients and duodenal perforation in one. We conclude that Nd:YAG-laser photocoagulation does not benefit patients with acute upper gastrointestinal bleeding from peptic ulcers.

Acute Disease↗

Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis.

BACKGROUND: Current guidelines recommend that patients at risk for ulcer disease who require treatment for arthritis receive nonsteroidal antiinflammatory drugs (NSAIDs) that are selective for cyclooxygenase-2 or the combination of a nonselective NSAID with a proton-pump inhibitor. We assessed whether celecoxib would be similar to diclofenac plus omeprazole in reducing the risk of recurrent ulcer bleeding in patients at high risk for bleeding. METHODS: We studied patients who used NSAIDs for arthritis and who presented with ulcer bleeding. After their ulcers had healed, we randomly assigned patients who were negative for Helicobacter pylori to receive either 200 mg of celecoxib twice daily plus daily placebo or 75 mg of diclofenac twice daily plus 20 mg of omeprazole daily for six months. The end point was recurrent ulcer bleeding. RESULTS: In the intention-to-treat analysis, which included 287 patients (144 receiving celecoxib and 143 receiving diclofenac plus omeprazole), recurrent ulcer bleeding occurred in 7 patients receiving celecoxib and 9 receiving diclofenac plus omeprazole. The probability of recurrent bleeding during the six-month period was 4.9 percent (95 percent confidence interval, 3.1 to 6.7) for patients who received celecoxib and 6.4 percent (95 percent confidence interval, 4.3 to 8.4) for patients who received diclofenac plus omeprazole (difference, -1.5 percentage points; 95 percent confidence interval for the difference, -6.8 to 3.8). Renal adverse events, including hypertension, peripheral edema, and renal failure, occurred in 24.3 percent of the patients receiving celecoxib and 30.8 percent of those receiving diclofenac plus omeprazole. CONCLUSIONS: Among patients with a recent history of ulcer bleeding, treatment with celecoxib was as effective as treatment with diclofenac plus omeprazole, with respect to the prevention of recurrent bleeding. Renal toxic effects are common in high-risk patients receiving celecoxib or diclofenac plus omeprazole.

Anti-Inflammatory Agents, Non-Steroidal↗

Endoscopic treatment of bleeding gastric varices by N-butyl-2-cyanoacrylate (Histoacryl) injection: long-term efficacy and safety.

BACKGROUND: The long-term efficacy and safety of the endoscopic injection of N-butyl-2-cyanoacrylate (Histoacryl) were evaluated to define its role as the initial treatment for bleeding gastric varices. METHODS: Ninety patients with bleeding gastric varices underwent endoscopic injections of Histoacryl for hemostasis within a 6-year period. Histoacryl was injected intravariceally as a 1:1 mixture with Lipiodol. Among the 90 patients, 5 had active bleeding and 85 had recent bleeding. Most of the varices were large (F2 or F3, 85 cases). The most common locations were the fundus and the posterior wall of the proximal body (94.4%). After Histoacryl injection, patients were followed endoscopically with retreatment as necessary. RESULTS: The rate of hemostasis at 1 week was 94.4%. Recurrent bleeding occurred in 23.3% of the patients from 3 days to 16 months after the initial injection. Recurrent bleeding was stopped with reinjections of Histoacryl in 16.7% of the patients. The rate of definitive hemostasis was 93.3% (84 of 90). The treatment failure-related mortality rate was 2.2% (2 of 90). To date, 35 patients have died, mostly as a result of malignancy or liver failure, and 55 are still alive. The determining factor for long-term survival was the underlying disease leading to portal hypertension. There were few long-term complications except for Histoacryl cast extrusion-related mucosal defects. CONCLUSIONS: Endoscopic injection of Histoacryl is highly effective for the treatment of bleeding gastric varices, with rare complications both acutely and long term. This treatment modality is appropriate as the first choice for bleeding gastric varices.

Adult↗

Prophylactic clip application does not decrease delayed bleeding after colonoscopic polypectomy.

BACKGROUND: The most common major complication of colonoscopic polypectomy is postpolypectomy hemorrhage. Although several factors have been implicated in the occurrence of hemorrhage, accurate prediction of delayed bleeding remains difficult. This randomized controlled trial evaluated the efficacy of prophylactic clip application for prevention of delayed postpolypectomy bleeding. METHODS: Postpolypectomy ulcers created by colonoscopic removal of polyps (mean size 7.8 [4.0] mm) with the endoscopic mucosal resection technique were randomly assigned to prophylactic clip placement (n = 205) or no clip (n = 208). Baseline characteristics of the patients and polyps excised were comparable between the groups. Delayed bleeding was defined as the postprocedure passage of bloody stool or massive hematochezia. The site of delayed bleeding was identified at emergent colonoscopy. RESULTS: Delayed bleeding was identified from 2 ulcers in each group from 1 to 4 days after resection (mean 2.3 days). Delayed bleeding occurred from 0.98% of ulcers in the clip group and 0.96% in the non-clip group (p > 0.9999). No patient with delayed bleeding required transfusion or surgery. CONCLUSIONS: Prophylactic clip placement did not decrease the occurrence of delayed bleeding after colonoscopic polypectomy.

Adenocarcinoma↗

Transvaginal ultrasonography of the endometrium in women with postmenopausal bleeding: is it always necessary to perform an endometrial biopsy?

OBJECTIVE: This study was undertaken to evaluate whether it was possible to abstain from performing an endometrial biopsy when endometrial thickness according to transvaginal ultrasonography was </=4 mm in women with postmenopausal bleeding or irregular bleeding during hormone replacement therapy. STUDY DESIGN: Transvaginal ultrasonography was performed in 361 women aged >/=50 years who were referred because of postmenopausal bleeding or irregular bleeding during hormone replacement therapy. If endometrial thickness was </=4 mm, a Papanicolaou cervical smear was performed and the woman was reexamined with transvaginal ultrasonography after 4 and 12 months. Subjects were also instructed to return if they had recurrent bleeding, in which case transvaginal ultrasonography was performed and an endometrial biopsy specimen was obtained. Women with an endometrial thickness >/=5 mm underwent either curettage or endometrial biopsy. RESULTS: One hundred sixty-three women had an endometrial thickness </=4 mm. In this group one endometrial cancer that was missed by ultrasonography was diagnosed by cervical cytologic examination and two adnexal malignancies were diagnosed by ultrasonography. Endometrial malignancy was diagnosed in 0.6% of the women with an endometrial thickness </=4 mm. Endometrial biopsy was performed because of recurrent bleeding in 6.1% of cases and because of endometrial thickening in 8.1%. No cancer or hyperplasia was subsequently diagnosed among the women with an endometrial thickness </=4 mm. Endometrial cancer was diagnosed in 18.7% of the women with an endometrial thickness >/=5 mm. The corresponding figure when atypical hyperplasia and endometrial metastases were included was 20. 2%. CONCLUSION: If the false-negative rate of endometrial biopsy techniques is taken into account, then the combination of transvaginal ultrasonography and cervical cytologic examination is an adequate form of management for women with postmenopausal bleeding or irregular bleeding during hormone replacement therapy as long as endometrial thickness is </=4 mm. A randomized prospective study is necessary to verify this finding.

Biopsy↗

Massive lower gastro-intestinal bleeding due to small bowel diverticula. A report of two cases.

Gastro-intestinal bleeding from the small bowel is a rare entity. It is difficult to determine the source of bleeding because of the unavailability of routine small bowel endoscopy. The most common reasons for bleeding from the small bowel are tumours, arteriovenous malformations and inflammatory bowel diseases. Diverticula of the small bowel are very uncommon. We present two cases of gastro-intestinal bleeding due to small bowel diverticula. Both of them were diagnosed on laparotomy. One had a short segment of small bowel, with six diverticula, which was resected. The second case had a long segment of small bowel with multiple diverticula. This patient was treated by isolating and excising the bleeding diverticulum. Haemodynamically unstable lower gastro-intestinal bleeding mandates exploratory laparotomy. Mesenteric angiography and Tc 99 labelled erythrocyte scintigraphy can detect the bleeding site. Intra-operative endoscopy can be performed safely via an enterotomy and can localize the bleeding site.

Aged↗

Dysfunctional uterine bleeding. Clarifying its definition, mechanisms, and management.

"Dysfunctional uterine bleeding" is not a generic term for abnormal uterine bleeding. Rather, it refers solely to bleeding caused by an ovarian endocrinopathy. Estrogen withdrawal and inappropriately sustained estrogen production are the two mechanisms responsible. The latter mechanism produces estrogen breakthrough bleeding, which is common in women with chronic anovulation. Treatment of estrogen withdrawal bleeding depends on when in the menstrual cycle bleeding occurs. Anovulatory bleeding is best treated with progestin. Estrogen therapy is contraindicated, except in patients with profuse anovulatory bleeding unresponsive to progestin treatment, because it increases the risk of endometrial hyperplasia and cancer.

Adenocarcinoma↗

Factors associated with failure of endoscopic injection haemostasis in bleeding peptic ulcers.

BACKGROUND: The effectiveness of a submucosal injection of adrenaline solution in endoscopic haemostasis is well documented in patients suffering from peptic ulcer bleeding. After treatment, however, a significant number of patients continue to bleed or rebleed, and require emergency surgical intervention. The aim of this study was to define factors associated with the failure of endoscopic injection haemostatic therapy in peptic ulcer bleeding. METHODS: In the period 1992 to 1998, we prospectively studied all patients suffering from peptic ulcer bleeding and identified endoscopically as being either bleeding actively or carrying a visible vessel. A total of 427 patients (343 men and 84 women; mean age 58.6 +/- 16.6 years) were all subjected to endoscopic injection with adrenaline solution on an emergency basis. Patients who eventually required surgical intervention for permanent haemostasis were considered as endoscopic haemostasis failures, whereas those who did not were considered as endoscopic treatment successes. We evaluated all clinical and endoscopic parameters that might have been related to failure of endoscopic injection therapy. RESULTS: Endoscopic injection haemostasis was successful in 341 patients (79.9%) and a failure in 86 (20.1%) who finally underwent emergency surgical haemostasis. On analysing the examined parameters, failure was significantly related to shock on admission (OR 2.31, 95% CI 1.33, 6.97), spurt bleeding at endoscopy (OR 2.45, 95% CI 1.51, 3.98), posteriorly located duodenal ulcer (OR 2.48, 95% CI 1.37, 7.01) and anastomotic ulcer (OR 3.39, 95% CI 1.37, 7.29). Endoscopic injection haemostasis therapy was less effective in patients with chronic ulcers compared to those who had acute NSAID-related ulcers. A history of peptic ulcer (OR 1.57, 95% CI 1.14, 3.05), previous peptic ulcer bleeding (OR 2.45, 95% CI 1.51, 3.98) or non-use of NSAIDs (OR 2.81, 95% CI 1.33, 4.62) were negative predictors for the outcome of endoscopic haemostasis. CONCLUSION: With the use of specific clinical and endoscopic characteristics it is possible to define a subgroup of high-risk patients for continued bleeding or rebleeding despite endoscopic injection therapy. These patients may be candidates for intensive monitoring, early surgical intervention or possibly complementary endoscopic haemostatic methods.

Epinephrine↗

Probability of early pregnancy loss in women with vaginal bleeding and a singleton live fetus at ultrasound scan.

Bleeding is a common feature of early pregnancy affecting about one-fifth of pregnant women in the first trimester. The chance of miscarriage after bleeding and a live fetus at scan has not previously been defined precisely. The purpose of this study was to evaluate the outcome of early pregnancies with a viable singleton fetus that had been complicated by bleeding. A prospective study was performed on 370 women with a singleton live fetus who had presented to the early pregnancy assessment clinic (EPAC) with vaginal bleeding. Women were grouped into light, moderate and heavy loss according to the self-assessed degree of vaginal bleeding. The women were also categorised according to the presence or absence of an intrauterine haematoma. The overall spontaneous miscarriage rate in the study was 11.1%; almost 90% of pregnancies continued to viability. Women with moderate or heavy bleeding had more than twice the rate of miscarriage compared with those with light bleeding. A total of 14% of the women had an intrauterine haematoma and those women were 2.6 times more likely to miscarry than those without (23% vs 9%). This relationship appeared to hold true even after controlling for blood loss. The data presented can be used to guide women with a live fetus about the chance of miscarriage after an episode of vaginal bleeding. We propose that a large multi-centre study should be undertaken to define precisely the risk miscarriage for each gestational week according to a range of clinical and ultrasound characteristics.

Abortion, Spontaneous↗

A low-cost and simple method to stop intraoperative leakage-type bleeding: use of the vancomycin-oxidized regenerated cellulose (ORC) sandwich.

Intraoperative bleeding may cause life-threatening complications in patients if such bleeding cannot be brought under control. Various materials are available for stopping such bleeding. However, there are some difficulties in the acquisition and application of these materials. The aim of this study was to investigate the efficiency of the low-cost and simple-to-prepare vancomycin-oxidized regenerated cellulose (ORC) sandwich in surgical bleeding control. Thirty New Zealand rabbits were used for this purpose. The animals were separated into three groups as group 1 (n = 10), control group; group 2 (n = 10), oxidized regenerated cellulose (ORC) group; and group 3 (n = 10), vancomycin-ORC sandwich group. Left thoracotomies were performed on the rabbits under general anesthesia, and bleeding was created in the parietal pleura. The amount of bleeding in the groups was measured and compared. The amount of bleeding in the group in which the vancomycin-ORC sandwich was used was found to be less, compared to the other two groups. According to these results, we conclude that the vancomycin-ORC sandwich can be used safely in the control of intraoperative leakage-type bleeding, as the vancomycin-ORC sandwich is a low-cost, easily applied, and easily acquired material.

Animals↗

Changes in endometrial blood vessels in the endometrium of women with hormone replacement therapy-related irregular bleeding.

BACKGROUND: Irregular bleeding affects up to 60% of hormone replacement therapy (HRT) users. The mechanism of this bleeding is not understood. Reduced endometrial microvascular integrity appears to underlie breakthrough bleeding in pre-menopausal women and the aim of this study was to establish whether similar changes are seen in HRT users and hence to elucidate a possible mechanism of irregular bleeding. METHODS: Endometrium from 34 HRT users with amenorrhoea, irregular bleeding or regular bleeding was assessed for endometrial endothelial cell density (anti-CD34), number of blood vessels per mm(2), vascular basal lamina components (laminin, collagen IV and heparan sulphate proteoglycan) and in 32 subjects and 23 controls for perivascular smooth muscle alpha (SMA). Findings were compared with a control population of 29 post-menopausal women not using HRT, other sex steroids or tamoxifen and with no vaginal bleeding. Staining intensity was assessed in a blinded fashion in all immunohistochemical studies. RESULTS: Four significant differences in endometrial blood vessels were observed between HRT users and controls: (i) a significantly lower density of endometrial endothelial cells (EC staining for CD34) per mm(2) was present in HRT users compared with controls (P < 0.001); (ii) endothelial cells (EC) were predominantly organized within blood vessels (83%) in controls but in HRT users EC were dispersed in the tissues with only 29% in organized vessels (P <0.001); (iii) supportive perivascular cell SMA was significantly reduced in 23 post-menopausal HRT users compared with 23 post-menopausal controls (n = 29, P = 0.013) and (iv) an atrophic or inactive histological pattern of endometrium was more frequently seen in the controls (P < 0.001). CONCLUSIONS: These findings support the hypothesis that exposure to HRT profoundly alters endometrial blood vessels, reducing structural integrity thereby predisposing to irregular bleeding in HRT users.

Actins↗

Expression of vascular endothelial growth factors and their receptors in human endometrium from women experiencing abnormal bleeding patterns after prolonged use of a levonorgestrel-releasing intrauterine system.

BACKGROUND: Menstrual bleeding disturbances are a common initial complaint among users of the levonorgestrel-releasing intrauterine system (LNG-IUS). In this study, women who experienced bleeding disturbances recurring after a previous period of problem-free use and who therefore wanted removal of their LNG-IUD were investigated. Vascular endothelial growth factors (VEGFs) and their receptors are thought to be involved in normal endometrial angiogenesis. The aim of the study was to elucidate the possible association of these VEGF and receptors with bleeding disturbances among users of LNG-IUS. METHODS: Endometrial biopsies were obtained from users of the LNG-IUS who complained of bleeding disturbances (n = 17) and from women without such problems (n = 14). The endometrial expression of these VEGFs and their receptors was analysed using immunohistochemistry. RESULTS: Endometrial endothelial cells from LNG-IUS users with menstrual bleeding disturbances exhibited significantly higher immunoreactivity for VEGFR-1 and VEGFR-3 than those from women without bleeding disturbances. Stromal cells showed significantly lower immunoreactivity for VEGF-A in samples from LNG-IUS users with bleeding disturbances than in those without. CONCLUSION: Changes in the expression of these angiogenic growth factors and their receptors in LNG-IUS-exposed endometrium might be involved in the formation of fragile and dysfunctional blood vessels that subsequently give rise to bleeding disturbances.

Adult↗

Tranexamic acid is beneficial as adjunctive therapy in treating major upper gastrointestinal bleeding in dialysis patients.

BACKGROUND: In a pilot, non-randomized trial we tested the efficacy of tranexamic acid (TXA), a potent fibrinolytic inhibitor, as adjunctive therapy in standard treatment of major upper gastrointestinal bleeding in dialysis patients. METHODS: Twenty consecutive patients (12 male, eight female; 63+/-8 years) with 36 episodes of major upper gastrointestinal bleeding were included in the study. In 16 episodes of bleeding TXA was used (in a dosage of 20 mg intravenously, followed for the next 4 weeks by 10 mg/kg/48 h orally), whereas in 20 other cases of bleeding, TXA was not used. The decision to use TXA was left to the attending physician's clinical judgement, resulting in all the more severe cases of bleeding being treated with TXA. RESULTS: Treatment including TXA was shown to be beneficial (relative to cases not treated with TXA) in terms of decreasing the rate of early re-bleeding (in the first week, 0 vs 6, P<0.05), the rate of early and late re-bleeding (in the first month, 1 vs 8, P<0.05), the rate of repeated endoscopic procedures (in the first month, 1 vs 8, P<0.05) and the number of blood transfusions needed (in the first month, 1.4+/-1.3 vs 2.6+/-1.5 units, P<0.05). CONCLUSIONS: The results of this pilot study suggest that TXA can be beneficial in the treatment of major upper gastrointestinal bleeding in dialysis patients. This remains to be definitely confirmed in a randomized study.

Aged↗

Clinical aspects of bleeding complications in cirrhotic patients.

Liver disease is a frequent cause of haemostatic abnormalities, which may lead to overt or occult bleeding. Clinical manifestations of hepatic coagulopathy include upper and lower gastrointestinal haemorrhage, easy bruising and bleeding from gums, nose or the female genital tract. The most significant bleeding problem among patients with chronic liver disease is blood loss due to portal hypertension. About 30% of subjects with oesophageal or gastric varices resulting from cirrhosis have an episode of gastrointestinal bleeding in their lifetime. Risk factors for the first episode of variceal bleeding include the severity of liver dysfunction, large varices, and the presence of endoscopic red colour signs. Bacterial infection in patients with variceal haemorrhage may be critical in triggering bleeding. Nongastrointestinal bleeding events, either spontaneous or induced by minor trauma, are also a common complication of advanced cirrhosis. In women, for instance, dysfunctional uterine bleeding may become so severe that hysterectomy is required. In addition, invasive diagnostic tests (mostly solid tissue biopsies) and surgical procedures have a high risk of haemorrhage and are sometimes withheld in cirrhotic patients for fear of complications. In patients with portal hypertension, surgical procedures aggravate the injury of the hepatic parenchyma and may worsen the condition.

Bacterial Infections↗

Evaluation of technetium-99m DTPA for localization of site of acute upper gastrointestinal bleeding.

Intravenous Tc-99m DTPA was evaluated in 34 patients with active upper gastrointestinal bleeding. Active bleeding was detected in 25 patients: nine in the stomach, 12 in the duodenum, and four from esophageal varices. No active bleeding was seen in nine patients (two gastric ulcers and seven duodenal ulcers). Results were correlated with endoscopic and/or surgical findings. All completely correlated except: 1) one case of esophageal varices in which there was disagreement on the site, 2) three cases of duodenal ulcers that were not bleeding on endoscopy but showed mild oozing on delayed images and 3) one case of gastric ulcer, in which no bleeding was detected in the Tc-99m DTPA study, but was found to be bleeding at surgery 24 hours later. The Tc-99m DTPA study is a reliable method for localization of upper gastrointestinal bleeding with an agreement ratio of 85%. This method also can be used safely for follow-up of patients with intermittent bleeding. It is less invasive than endoscopy, is easily repeatable, and has the same accuracy.

Acute Disease↗

Does antacid prophylaxis prevent upper gastrointestinal bleeding in critically ill patients?

Sixty-five surgical ICU patients at high risk of developing acute erosive gastritis and bleeding received prophylactic antacid treatment to maintain a gastric pH of at least 5.0. A similar control group of 61 patients received no specific prophylaxis. All patients in both groups developed microscopic bleeding; however, microscopic bleeding did not influence outcome. In the control group, eight (13.1%) patients developed moderate visible bleeding, as compared to seven (10.8%) patients in the antacid group, an insignificant difference. A single patient in the control group developed severe GI bleeding due to acute erosive gastritis. Antacid prophylaxis did not prevent macroscopic bleeding and there was no correlation between the number of risk factors in individual patients and the rate of upper GI bleeding. We conclude that antacid is not required to prevent upper GI bleeding in high-risk critically ill patients.

Adolescent↗

Prospective study of clinical bleeding in intensive care unit patients.

We investigated prospectively clinical bleeding in 1,328 consecutive patients admitted to a medical/surgical ICU over 1 yr. One hundred thirty-eight (10.4%) patients bled after ICU admission, and an additional 388 (29.2%) bled coincident with admission. The upper GI tract was the site of bleeding in 34.8% of patients whose bleeds commenced in the ICU, and accounted for 22% of total sites. Patients with clinical bleeding after ICU admission had a significantly (p less than .001) higher likelihood of death than those who did not bleed, and those with multiple bleeding sites had a higher mortality (54.9%) than those with single sites (31%) (p less than .006). Multiple logistic regression analyses revealed that risk ratios (RR) for bleeding after ICU admission were mechanical ventilation (RR = 1.82), nutritional failure (RR = 3.45), acute renal failure (RR = 3.36), antiulcer medication (RR = 3.36), and anticoagulants (RR = 4.19). No antibiotics could be specifically incriminated. This study defines the scope, characteristics, and importance of bleeding in ICU patients and establishes risk factors.

Aged↗

Seasonality in the prevalence of acute upper gastrointestinal bleeding.

The seasonal fluctuations of acute upper gastrointestinal bleeding treated from 1991 to 1996 in Patras, Greece, were analyzed retrospectively. During that period, 1992 patients with acute upper gastrointestinal bleeding were admitted to our hospital. After patients who were not residents of the region served by our hospital were excluded, the remaining 1879 cases were reviewed. We observed seasonal fluctuation with low prevalence in winter and an increase in spring and autumn with two peaks in April and October (p < 0.00001). The seasonal prevalence parallels that of duodenal ulcer bleeding, which follows a similar fluctuation (p < 0.00001). Bleeding due to gastric ulcers or other causes presented no periodicity. Seasonal fluctuation, both in total numbers of upper gastrointestinal bleeding and in duodenal ulcer bleeding, was statistically significant only in patients not receiving nonsteroidal anti-inflammatory drugs (p < 0.00001). We conclude that upper gastrointestinal bleeding shows a seasonal fluctuation parallel to duodenal ulcer bleeding and is not related to nonsteroidal anti-inflammatory drugs. The seasonal pattern supports the traditional view of duodenal ulcer exacerbations.

Acute Disease↗