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Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study.

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) have been suspected of increasing the risk of bleeding. We examined the risk of upper gastrointestinal tract (GI) bleeding with use of antidepressant medication. METHODS: All users of antidepressants in the county of North Jutland, Denmark, from January 1, 1991, to December 31, 1995, were identified in the Pharmaco-Epidemiologic Prescription Database of North Jutland. In the Hospital Discharge Register, hospitalizations for upper GI bleeding were searched among the 26 005 users of antidepressant medications and compared with the number of hospitalizations in the population of North Jutland who did not receive prescriptions for antidepressants. RESULTS: During periods of SSRI use without use of other drugs associated with upper GI bleeding, we observed 55 upper GI bleeding episodes, which was 3.6 times more than expected (95% confidence interval, 2.7-4.7), corresponding to a rate difference of 3.1 per 1000 treatment years. Combined use of an SSRI and nonsteroidal anti-inflammatory drugs or low-dose aspirin increased the risk to 12.2 (95% confidence interval, 7.1-19.5) and 5.2 (95% confidence interval, 3.2-8.0), respectively. Non-SSRIs increased the risk of upper GI bleeding to 2.3 (95% confidence interval, 1.5-3.4), while antidepressants without action on the serotonin receptor had no significant effect on the risk of upper GI bleeding. The risk with SSRI use returned to unity after termination of SSRI use, while the risks were similarly increased during periods of use and nonuse of non-SSRIs. CONCLUSION: Selective serotonin reuptake inhibitors increase the risk of upper GI bleeding, and this effect is potentiated by concurrent use of nonsteroidal anti-inflammatory drugs or low-dose aspirin, whereas an increased risk of upper GI bleeding could not be attributed to other types of antidepressants.

Aged↗

Complete intraoperative small-bowel endoscopy in the evaluation of occult gastrointestinal bleeding using the sonde enteroscope.

OBJECTIVE: To review our experience with intraoperative small-bowel Sonde enteroscopy in evaluating occult bleeding in the small intestine. DESIGN: Retrospective study with 100% follow-up. SETTING: University-affiliated, tertiary-care teaching hospital. PATIENTS: Sixteen consecutive patients referred with occult gastrointestinal bleeding in whom esophagogastro-duodenoscopy , push enteroscopy, and colonoscopy had failed to identify the source of bleeding. Fourteen of the 16 patients had required one or more transfusions. MAIN OUTCOME MEASURE: Completeness of visualization, diagnostic accuracy, and complications of the procedure and follow-up for recurrent bleeding. RESULTS: In all 16 patients, intraoperative Sonde enteroscopy allowed visualization of the entire small bowel. In 14 of the 16, it revealed the cause of bleeding, which was ileal angiodysplasia in three patients, ileal ulcers in six patients, neoplasia in two patients, and ileal ulcers caused by Crohn's disease, small-intestinal enteropathy and varices caused by portal hypertension, and radiation stricture in one patient each. Two patients had normal small bowel mucosa. The patients with mucosal disease underwent small-bowel resection or oversewing of bleeding sites. Two surgical complications occurred: prolonged postoperative ileus (one patient) and small-bowel obstruction that resolved without surgery (one patient). Two of the patients with angiodysplasia had recurrent bleeding postoperatively. CONCLUSIONS: Intraoperative Sonde enteroscopy is safe and effective in localizing small-intestinal bleeding sites, providing complete visualization of the small-bowel mucosa without enterotomy while avoiding the trauma that can be caused by push endoscopy. It is the diagnostic assessment of choice in selected patients with occult gastrointestinal bleeding of presumed small-bowel origin.

Adult↗

Non-steroidal anti-inflammatory drugs and perioperative bleeding in paediatric tonsillectomy.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for pain relief following tonsillectomy in children. However, as they inhibit platelet aggregation and prolong bleeding time, they could cause increased perioperative bleeding. The overall risk remains unclear. OBJECTIVES: The primary objective of this review was to assess the effects of NSAIDs on bleeding for paediatric tonsillectomy. There is good evidence (Kokki 2003; Romsing 1997) to show that NSAIDs are effective analgesics in children. It was not the remit of our review to question this, but rather to assess the risk of bleeding when NSAIDs are used for pain relief following paediatric tonsillectomy. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2004); MEDLINE (inception until August 2004); EMBASE (from inception until August 2004), Current Problems (produced by the UK Medicines Control Agency); MedWatch (produced by the US Food and Drug Administration) and the Australian Adverse Drug Reactions Bulletin in December 2001. The Cochrane Anaesthesia Review Group's handsearch co-ordinator performed handsearching as required. We also contacted manufacturers and researchers in the field. SELECTION CRITERIA: We included randomized controlled trials assessing NSAIDs in children up to and including 16 years of age, undergoing elective tonsillectomy or adenotonsillectomy. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted the data. We contacted study authors where necessary for additional information. We also collected information on adverse effects from the trials. MAIN RESULTS: We included 13 trials involving 955 children. All included trials compared NSAIDs with other analgesics or placebo and looked at bleeding requiring surgical intervention. NSAIDs did not significantly alter number of perioperative bleeding events requiring surgical intervention; Peto odds ratio 1.46 (95% confidence interval 0.49 to 4.40). Seven trials involving 471 children looked at bleeding not requiring surgical intervention. NSAIDs did not significantly alter number of perioperative bleeding events not requiring surgical intervention; Peto odds ratio 1.23 (95% confidence interval 0.44 to 3.43). Ten trials involving 837 children looked at post-operative nausea and vomiting. There was less nausea and vomiting when NSAIDs were used as part of the analgesic regime, compared to when NSAIDs were not used; Odds ratio 0.40 (95% confidence interval 0.23 to 0.72). AUTHORS' CONCLUSIONS: NSAIDs did not cause any increase in bleeding requiring a return to theatre. There was significantly less nausea and vomiting when NSAIDs were used compared to alternative analgesics.

Adolescent↗

Effect of feed and bleed rate on hybridoma cells in an acoustic perfusion bioreactor: part I. Cell density, viability, and cell-cycle distribution.

For the development of optimal perfusion processes the effect of the feed and bleed rate on cell growth in a perfusion bioreactor was studied. The viable-cell density, viability, growth, death, and lysis rate and cell-cycle distribution of a hybridoma cell line producing an IgG1 were studied over a range of specific feed and bleed rates. It was found that the feed and bleed rates applied in the different cultures could be divided into two regions based on the viable-cell density and cell-cycle distribution. The cultures in the first region, low feed rates (0.5 and 1.0 d(-1)) combined with low bleed rates (0.05 and 0.10 d(-1)), were nutrient-limited, as an increase in the feed rate resulted in an increase in the viable-cell density. The cultures in the second region, high feed and bleed rates, were nonnutrient-limited. In this region the viable-cell density decreased more or less linearly with an increase in the bleed rate and was independent of the feed rate. This suggests that the cells were limited by a cell-related factor. Comparison of Trypan-blue dye-exclusion measurements and lactate-dehydrogenase activity measurements revealed that cell lysis was not negligible in this bioreactor set-up. Therefore, lactate-dehydrogenase activity measurements were essential to measure the death rate accurately. The specific growth rate was nearly constant for all tested conditions. The viability increased with an increase of the bleed rate and was independent of the feed rate. Furthermore, the specific productivity of monoclonal antibody was constant under all tested conditions. For the optimal design of a perfusion process it should first be established whether viability is an important parameter. If not, a bleed rate as low as possible should be chosen. If low viabilities are to be avoided, the bleed rate chosen should be higher, with the value depending on the desired viability. Next, the feed rate should be set at such a rate that the cells are just in the nonnutrient-limited region.

Acoustics↗

Somatostatin in the treatment of severe upper gastrointestinal bleeding: a multicentre controlled trial.

To evaluate the effectiveness of somatostatin versus combined cimetidine and pirenzepine in the treatment of upper gastrointestinal (GI) bleeding of peptic origin, a multicentre controlled, prospective, randomized and double blind trial has been undertaken in 60 subjects. Strict selection criteria were followed. All subjects were diagnosed by endoscopy during the first 18 h after admission. Endoscopic stigmata of recent haemorrhage were also evaluated. Sixty-five per cent of the subjects presented with severe upper GI bleeding (blood pressure less than or equal to 100 mmHg, pulse rate greater than or equal to 110, haematocrit less than or equal to 30 per cent), and in 71.6 per cent stigmata were found. Thirty patients (Group 1) received a somatostatin infusion (250 micrograms/h continuously during 120 h) and 30 patients (Group 2) received cimetidine (200 mg IV every 4 h for 5 days) and pirenzepine (10 mg IV every 8 h for 5 days). Both groups were homogeneous for sex, age, backgrounds, bleeding source, grade of bleeding (moderate or severe) and presence or not of stigmata. Bleeding stopped in 27 subjects of Group 1 (90 per cent and in 20 subjects of Group 2 (66.67 per cent) (P less than 0.05, chi 2 test). The time until the bleeding stopped was significantly shorter in patients of group 1 (3.44 +/- 0.53 h) than in patients of group 2 (8.12 +/- 1.94 h) (P less than 0.05, Mann-Whitney U test). The number of blood units required for Group 1 (2.26 +/- 0.35) was significantly lower than the one required for Group 2 (3.90 +/- 0.51) (P less than 0.005, Wilcoxon test). Significant differences were not observed between the two groups regarding cross-over subjects, re-bleeding, surgery (P = 0.0635, Fisher's exact test) and hospital stay. The mortality of the trial was 5 per cent. There was no toxicity during somatostatin, cimetidine or pirenzepine infusion. In conclusion, somatostatin was more effective than cimetidine plus pirenzepine in the control of severe upper GI bleeding of peptic origin, with a lower interval time to stop bleeding and reduced transfusion requirements.

Cimetidine↗

Cost-effectiveness analysis of transjugular intrahepatic portosystemic shunt (TIPS) versus endoscopic therapy for the prevention of recurrent esophageal variceal bleeding.

For the prevention of recurrent esophageal variceal bleeding, studies show that patients treated with transjugular intrahepatic portosystemic shunt (TIPS) have lower rebleeding rates compared with endoscopic therapy. However, TIPS is associated with higher rates of portosystemic encephalopathy and possibly higher costs. The aim of this study was to conduct a cost-effectiveness analysis comparing TIPS with endoscopic sclerotherapy and endoscopic ligation for the prevention of recurrent esophageal variceal bleeding. Data for rates of rebleeding, death, complications, and crossover from endoscopy to TIPS were obtained from the literature. Costs for procedures and hospitalizations were obtained from two medical centers. Sensitivity analyses were performed varying probabilities of key variables. The patient population consisted of a hypothetical cohort of cirrhotic patients successfully treated for esophageal variceal bleeding with endoscopic sclerotherapy who received prophylactic sclerotherapy, ligation, or TIPS over 1 year. Endoscopic patients would receive propranolol. Mortality was similar for the three groups. The number of bleeds per patient for sclerotherapy, ligation, and TIPS would be 0.39, 0.32, and 0.07, respectively. The total annual costs per patient for sclerotherapy, ligation, and TIPS were $23,459, $23,111, and $26,275, respectively. The incremental cost per bleed prevented for TIPS compared with sclerotherapy and ligation was $8,803 and $12, 660, respectively. The incremental cost per bleed prevented for TIPS compared with sclerotherapy or ligation was sensitive to the cost of TIPS and the TIPS stenosis rate. Ligation had lower costs and lower recurrent bleeding rates than sclerotherapy. Compared with endoscopic therapy, TIPS leads to lower recurrent variceal bleeding rates and it is more cost effective in the short term for the prevention of recurrent esophageal variceal bleeding.

Cost-Benefit Analysis↗

Gastrointestinal bleeding of obscure origin: role of enteroclysis.

The purpose of this work was to assess retrospectively the yield of enteroclysis in 124 unselected patients presenting with obscure gastrointestinal bleeding. Of 1000 consecutive patients who were examined by enteroclysis 124 presented with occult gastrointestinal bleeding. A total of 61 patients with an unknown source of bleeding at the time of discharge, but with established gastrointestinal bleeding, were followed up by questionnaire to correlate the initial degree of bleeding with the incidence of recurrence of bleeding. Enteroclysis was normal in 109 cases. An abnormality was found subsequently be the cause of bleeding in the small intestine in 16 patients. Enteroclysis was positive in 14 cases, negative in 2 and false positive in 1. There was positive correlation between the initial degree of haemorrhage and the rate of recurrence. Enteroclysis detected the cause in 11% of patients who presented with bleeding of unknown origin. In patients with minor haemorrhage there was no recurrence of bleeding in most cases.

Adolescent↗

Failure of cyanoacrylate tissue glue (Flucrylate, MBR4197) to stop bleeding from experimental canine gastric ulcers.

A plastic tissue adhesive, trifluoroisopropyl 2-cyanoacrylate (Flucrylate (TM), MBR4197), was tested for hemostatic efficacy in acute laparotomy experiments using a canine model of acute bleeding gastric ulcer. An improved delivery system suitable for endoscopic use was developed. Hemostatic efficacy of the adhesive was tested in both briskly bleeding ulcers and in oozing ulcers after partial treatment with a heater probe. In pilot studies at laparotomy, primary and adjunctive cyanoacrylate therapy of 81 bleeding ulcers were evaluated in seven unheparinized foxhounds. Hemostasis was produced in 11% of ulcers treated with cyanoacrylate alone and in 31% of ulcers treated with cyanoacylate as an adjunctive after partial heater-probe treatment; no sham-treated control ulcers stopped bleeding under the conditions of the experiment. To evaluate Flucrylate (TM) using out standard heparinized ulcer model, a randomized study was performed in six heparinized foxhounds at laparotomy. Ulcers were randomized to treatment with cyanoacrylate alone, adjuctive cyanoacrylate, heater probe alone or untreated control. Sham-treated control ulcers or ulcers treated with cyanoacrylate alone did not stop bleeding; 42% of ulcers treated with cyanoacrylate as an adjunctive stopped bleeding; all ulcers treated with a heater probe stopped bleeding. In this experimental model of acute bleeding gastric ulcer, trifluoroisopropyl 2-cyanoacrylate (Flucrylate(TM),MBR4197) did not stop severe bleeding and was unpredictable as an adjunctive treatment.

Animals↗

An 8-year prospective experience with balloon tamponade in emergency control of bleeding esophageal varices.

The use of balloon tamponade in the emergency control of bleeding from esophageal varices is controversial. This paper reports a prospective study over an 8-year period in which balloon tamponade has been the sole means employed for the early control of bleeding varices. During 1972-1980 all patients referred to Prince Henry's Hospital with upper gastrointestinal bleeding were admitted to a special unit. Ninety-one had bleeding esophageal varices, and 17 were admitted on one or more occasions for bleeding for a total of 132 admissions. After early endoscopy, balloon tamponade was used during 103 of these admissions with failure to control bleeding on six occasions; five of these patients died from hemorrhage and the sixth recovered after emergency portacaval shunt. Another patient died from rebleeding not treated by tamponade. Reinsertion of the balloon for rebleeding was necessary on 28 occasions with successful control in all cases. Balloon tamponade was not used during 29 admissions because bleeding had ceased or the patient was considered to have terminal liver disease. In this group there were four deaths from severe liver disease and hemorrhage. Balloon tamponade was used in 78% of admissions and controlled bleeding in more than 90% of patients. This suggests that tamponade may be the method of choice early control of bleeding from esophageal varices.

Adult↗

Gastric bleeding and gastric secretion with sulindac and naproxen.

We have examined concurrent gastric secretory rates and bleeding by a gastric wash technique during treatment with naproxen, sulindac, and placebo. Twelve subjects, in each of 4 treatment periods, took either placebo, sulindac 200 mg, naproxen 250 mg, or naproxen 375 mg, twice a day for four days. Of the resultant 192 days (12 subjects, 4 drugs, 4 days/drug), two thirds of all days showed bleeding at a rate less than 0.5 ml/day; this low rate of bleeding was seen with all treatments. In spite of this minor bleeding, we were able to show statistically significantly less bleeding with placebo than with drugs; placebo never resulted in a maximum rate of bleeding for any subject. Distinctions between drugs on the basis of bleeding, however, were not possible. Correlations between outputs of acid and chloride were not significantly affected by any of these drugs. In contrast to previous results with aspirin, no correlation between rates of bleeding and gastric secretion could be established. The low water solubility of these drugs at the pH of gastric contents may account for their causing very little bleeding. In effect, the greater the gastric secretion of acid the less the absorption through the gastric mucosa.

Aspirin↗

Portal hypertension and bleeding esophageal varices.

Bleeding from esophageal varices exacts a high mortality and extraordinary societal costs. Prophylaxis--medication, sclerotherapy, or shunt surgery to prevent an initial bleeding episode--is ineffective. In patients who have bled from varices, endoscopic injection sclerotherapy can control acute bleeding in more than 90% of patients. Because recurrent bleeding frequently occurs and survival without definitive therapy is dismal, selection of a permanently effective treatment is mandatory once variceal bleeding has been controlled. Long-term injection sclerotherapy can be performed in compliant patients; it is relatively safe but is associated with a 30-50% rebleeding rate. Beta-blockers significantly reduce portal pressure and recurrent bleeding but have not been shown to diminish mortality from BEV. Portal decompressive surgery permanently halts bleeding in more than 90% of patients; the risk of operative mortality is high in decompensated cirrhotics, and long-term complications of encephalopathy and accelerated liver failure may limit indications for shunt surgery to good-risk cirrhotics who are not liver transplant candidates. Devascularization procedures have a low operative mortality and encephalopathy rate but unacceptably high rates of recurrent bleeding. Liver transplantation is curative therapy for bleeding esophageal varices and the associated underlying hepatic dysfunction; cost and availability of donor organs generally limit its use in this setting to variceal bleeders with end-stage liver disease not associated with active alcoholism.

Esophageal and Gastric Varices↗

Bleeding stomal varices. The role of local treatment.

The authors reviewed their experience with 12 patients (median age, 38 years; range, 24 to 66 years) who had bleeding stomal varices. Stomal variceal bleeding occurred between 1 and 11 years (median, 5.5 years) after creation of the stoma. Control of bleeding initially consisted of direct pressure; recurrent bleeding occurred in one patient who died before definitive therapy could be performed. The remaining 11 patients underwent a total of 18 additional procedures for control of bleeding stomal varices, including 9 local procedures, 8 portosystemic shunts, and 1 liver transplantation. Seven patients were dead of hepatic failure a median of 4 years (range, 1 to 9 years) after treatment. Recurrent bleeding occurred in three patients after local treatment and in one patient after a portosystemic shunt. Bleeding stomal varices are a manifestation of severe liver disease and portal hypertension. Although local procedures may be effective for initial control of bleeding, recurrent bleeding often occurs. Mortality is high because of the severity of the underlying liver disease.

Adult↗

Analysis of the colonoscopic findings in patients with rectal bleeding according to the pattern of their presenting symptoms.

Patients presenting with rectal bleeding were prospectively categorized according to the pattern of their presentation into those with outlet bleeding (n = 115), suspicious bleeding (n = 59), hemorrhage (n = 27), and occult bleeding (n = 68). All patients underwent colonoscopy and this was complete in 94 percent. There were 34 patients with carcinoma and 69 with adenomas greater than 1 cm diameter. The percentage of neoplasms proximal to the splenic flexure was 1 percent in outlet bleeding, 24 percent with suspicious bleeding, 75 percent with hemorrhage, and 73 percent with occult bleeding. Barium enema was available in 78 patients and was falsely positive for neoplasms in 21 percent and falsely negative in 45 percent. Colonoscopy is the investigation of choice in patients with suspicious, occult, or severe rectal bleeding. Bleeding of a typical outlet pattern may be investigated by flexible sigmoidoscopy.

Aged↗

Incidence and outcome of overt gastrointestinal bleeding in patients undergoing bone marrow transplantation.

The purpose of this study was to determine the prevalence, clinical patterns, and outcomes of gastrointestinal bleeding in consecutive patients treated at one bone marrow transplant center. We reviewed the clinical course of 579 consecutive bone marrow transplant recipients who underwent therapy from January 1986 through December 1993. These patients were evaluated for overt gastrointestinal bleeding, defined as hematemesis, melena, hematochezia, or a combination. Overt gastrointestinal bleeding was defined in 43 of 579 patients (7.4%), including 25 men and 18 women undergoing transplantation for hematologic disorders (N = 29) and solid tumors (N = 14). After high-dose cytotoxic chemotherapy, patients were given allogeneic (N = 10) or autologous (N = 33) hematopoietic progenitor cell support obtained from bone marrow, peripheral blood, or both. H2 blockers, sucralfate, or a combination were administered to all patients as prophylactic therapy. Bleeding manifestations included hematemesis(N = 24, melena (N = 8), hematochezia (N = 7), and combinations (N = 4). The median time from bone marrow infusion to the onset of overt gastrointestinal bleeding was 7.5 days (range: 0-45 days). Fourteen patients had evidence of orthostatic hypotension attributable to gastrointestinal bleeding. Esophagogastroduodenoscopy was performed in 26 patients; 18 had diffuse esophagitis and gastritis. Two patients with bleeding ulcers underwent successful electrocautery. Colonoscopy was performed in five patients and revealed a cecal ulcer in one subject, tumor recurrence in one patient, and colitis in another. No patients underwent surgical intervention. Only ine patient died as a result of gastrointestinal bleeding. Overt gastrointestinal bleeding is uncommon in patients undergoing bone marrow transplantation; most episodes are self-limited and do not contribute to overall mortality. Endoscopy is primarily diagnostic as most patients do not have lesions amenable to therapeutic procedures.

Adolescent↗

Aggressive colonoscopic approaches to lower intestinal bleeding.

The most obvious advantage of colonoscopy is to establish the diagnosis at any level of the colon by direct observation of the mucosal surface and identification of any active bleeding and or responsible lesions. It also enables therapeutic intervention. In a period of 18 years from 1973 to 1990, 230 emergency colonoscopic examinations were performed in 205 cases for evaluation of acute and severe bleeding from the lower intestinal tract. There were 108 men and 97 women. They appeared quite serious and needed constant medical supervision including shock treatment and blood transfusion. The ages of the patients varied from 5 months to 90 years old. There were 24 children in this series. Colonoscopy was performed within 48 hours after onset of anal bleeding. All examinations were done without fluoroscopy. It was necessary to reach the cecum in 66% of cases to determine the responsible lesions. Bleeding was identified in all except 11 cases (94.7%). Bleeding and the responsible lesions were both visualized in 147 cases (71.7%). The source of bleeding was located proximal to the ileocecal valve in 37 cases (18%). Much blood was found in the bowel which interfered observation in 14 cases. No bleeding nor lesions could be identified in 8 cases (3.9%). Most common causes of bleeding in adults were cancer, inflammatory lesions, ischemic colitis and vascular ectasia, while the most common cause of bleeding in children was juvenile polyp.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Upper gastrointestinal bleeding: etiology and management.

Upper gastrointestinal bleeding is a potentially fatal condition at times due to loss of large volumes of blood. Common sources of upper gastrointestinal bleeding in children include mucosal lesions and variceal hemorrhage (most commonly extra hepatic portal venous obstruction) and, in intensive care settings infections and drugs are other etiological factors associated with bleeding. Massive upper GI bleeding is life threatening and requires immediate resuscitation measures in the form of protection of the airways, oxygen administration, immediate volume replacement with ringer lactate or normal saline, transfusion of whole blood or packed cells and also monitoring the adequacy of volume replacement by central venous lines and urine output. Upper GI endoscopy is an effective initial diagnostic modality to localize the site and cause of bleeding in almost 85-90% of patients. Antacids supplemented by H2- receptor antagonists, proton pump inhibitors and sucralfate are the mainstay in the treatment of bleeding from mucosal lesion. For variceal bleeds, emergency endoscopy is the treatment of choice after initial haemodynamic stabilization of patient. If facilities for endoscopic sclerotherapy (EST) are not available, pharmacotherapy which decreases the portal pressure is almost equally effective and should be resorted to. Shunt surgery is reserved for patients who do not respond to the above therapy. Beta blockers combined with sclerotherapy have been shown to be the most effective therapy in significantly reducing the risk of recurrent rebleeding from varices as well as the death rates, as compared to any other modality of treatment. Based on studies among adult patients, presence of shock, co-morbidities, underlying diagnosis, presence of stigmata of recent hemorrhage on endoscopy and rebleeding are independent risk factors for mortality due to upper GI bleeding. Rebleeding is more likely to occur if the patient has hematemesis, liver disease, coagulopathy, hypotension and or anemia. There is a great need for conducting therapeutic trials as well as identifying predictors of outcome of upper GI bleeding in children to develop evidence based management protocols.

Adolescent↗

Clinical presentation of bleeding peptic ulcer in the elderly.

The aim of this study was to evaluate the characteristics and risk factors of bleeding peptic ulcer in elderly people. The histories of 206 consecutive patients (110 men and 96 women) with peptic ulcer were examined from hospital records. The ulcer was confirmed by endoscopy, surgery or autopsy. Clinical parameters were compared in different age groups. The mean age of the patients with bleeding ulcer (N = 105) was 65.5 years compared to 57.1 years in those without bleeding (N = 101) (p = 0.0001). In the univariate analysis, the duration of symptoms was shorter than seven days in 84% of bleeders compared to 40% of non-bleeders (p = 0.0001). Ninety percent of the bleeding patients were painfree, compared to 23% of patients without bleeding (p = 0.0001). Even when patients using nonsteroidal anti-inflammatory drugs (NSAIDs) were excluded, short duration of symptoms as well as absence of epigastric pain were significantly associated with bleeding. The bleeders tended to use more NSAIDs than non-bleeders, but the difference was significantly only in patients who had used NSAIDs for 30 or fewer days. Atypically located as well as giant ulcers bled more often than typically situated ulcers or smaller ulcers. In the logistic regression analysis, advanced age, short duration of symptoms and absence of epigastric pain independently predicted bleeding of peptic ulcer. In conclusion, although bleeding is a complication of peptic ulcer, it can also be considered a variant type of ulcer with specific characteristics. Old age seems to be an independent risk factor for bleeding, but it has no effect on the clinical presentation of the disease.

Adult↗

Determination of bleeding risk using genetic markers in patients taking phenprocoumon.

BACKGROUND: In patients on oral anticoagulation with warfarin, genetic variations of the cytochrome P 450-CYP2C9 have recently been associated with very low warfarin requirements. Patients needing low doses had an increased risk for bleeding complications. In Germany, phenprocoumon (having a similar metabolic pathway) is the most commonly employed vitamin K antagonist. Treatment is usually monitored by general practitioners (GPs). OBJECTIVES: To determine whether CYP2C9 variant alleles can serve as risk markers in general-practice patients anticoagulated with phenprocoumon. METHODS: All adult anticoagulated patients in 12 teaching general practices and one university outpatient clinic were to be recruited. Blood samples were taken from 185 patients during routine anticoagulation controls and tested for CYP2C9 mutations. Subjects answered a questionnaire concerning bleeding complications, drug intolerance, and personal and family medical history. Phenprocoumon dosages required for stable anticoagulation were recorded. Odds ratios (OR) with 95% confidence intervals (CI) were calculated based on 2-way cross-tabulations and multivariate logistic regression models, t-tests used where appropriate. RESULTS: Bleeding was reported by 19% of the patients, 2.2% of whom had suffered life-threatening bleeding. CYP2C9 variants were carried by 26.3% of 179 patients tested (17.9% *1/*2, 7.8% *1/*3, 0.6% *2/*3). While presence of a *2 allele was not associated with an increased risk (OR 0.35, CI 0.10-1.24), carriers of the rare *3 alleles had a higher risk of bleeding (OR 3.10, CI 1.02-9.40). With regard to bleeding, carrying CYP2C9*3 was highly specific (94%), though sensitivity was low at 17%; post-test probability of bleeding was 40%. CONCLUSIONS: CYP2C9*3 variants are associated with an increased bleeding risk in patients anticoagulated with phenprocoumon. Screening can identify patients with a high risk of bleeding. Appropriate clinical consequences (restricted indication for anticoagulation, careful induction, adjustment of target INR, closer monitoring or self-testing of INR) as well as the cost-effectiveness of screening for variant CYP2C9 with regard to patient outcomes should be subject of further research.

Aged↗