The outcome of children born with pulmonary atresia and intact ventricular septum in Sweden from 1980 to 1999.

OBJECTIVE: To study the outcome of all children born with pulmonary atresia and intact ventricular septum in Sweden between 1980 and 1999. DESIGN: Retrospective study of medical records with review of the initial, preoperative angiocardiographic and echocardiographic examinations. RESULTS: A total of 84 children were born with pulmonary atresia and intact ventricular septum, giving an incidence of 4.2 per 100,000 live births. In all, 77 were operated on with a 1-year survival rate of 75%. Thirty-six children had ventriculocoronary communications, with a 1-year survival rate of 50%. At the end of the study period, 52 children were alive, 32 with biventricular repair, and 19 with univentricular repair. Follow-up time was 14 days-20 years (median, 6 years). Statistical analysis of incremental risk factors for death showed statistical significance for low birth weight, male sex, muscular pulmonary atresia, and having a systemic-to-pulmonary shunt as the sole initial intervention. CONCLUSION: Complete national data of all patients born with pulmonary atresia and intact ventricular septum during 1980-1999 in Sweden revealed a total mortality in accordance with previous reports for results for surgery. Further improvements demand a thorough preoperative investigation of the cardiac anatomy, particularly of the ventriculocoronary communications, to enable right ventricular decompression whenever possible.

Esomeprazole improves healing and symptom resolution as compared with omeprazole in reflux oesophagitis patients: a randomized controlled trial. The Esomeprazole Study Investigators.

BACKGROUND: The pharmacologic profile of the new proton pump inhibitor esomeprazole has demonstrated advantages over omeprazole that suggest clinical benefits for patients with acid-related disease. METHODS: 1960 patients with endoscopy-confirmed reflux oesophagitis (RO) were randomized to once daily esomeprazole 40 mg (n=654) or 20 mg (n=656), or omeprazole 20 mg (n=650), the standard recommended dose for RO, for up to 8 weeks in a US, multicentre, double-blind trial. The primary efficacy variable was the proportion of patients healed at week 8. Secondary variables included healing and heartburn resolution at week 4, time to first resolution and sustained resolution of heartburn, and per cent of heartburn-free days and nights. Safety and tolerability were also evaluated. RESULTS: Significantly more patients were healed at week 8 with esomeprazole 40 mg (94.1%) and 20 mg (89.9%) vs. omeprazole 20 mg (86.9%), using cumulative life table estimates, ITT analysis (each P < 0.05). Esomeprazole 40 mg was also significantly more effective than omeprazole for healing at week 4 and for all secondary variables evaluating heartburn resolution. The most common adverse events in all treatment groups were headache, abdominal pain and diarrhoea. CONCLUSION: Esomeprazole was more effective than omeprazole in healing and symptom resolution in GERD patients with reflux oesophagitis, and had a tolerability profile comparable to that of omeprazole.

Efficacy of omeprazole for the treatment of symptomatic acid reflux disease without esophagitis.

BACKGROUND: Up to three quarters of patients with gastroesophageal reflux disease (GERD) have symptoms, such as heartburn, but no macroscopic evidence of erosive esophagitis, making symptomatic GERD a common clinical problem in the primary care setting. OBJECTIVE: To compare the efficacy and safety of omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; and placebo in the treatment of symptomatic GERD without erosive esophagitis. METHODS: Patients with a history of heartburn (> or =12 months) and episodes of moderate to severe heartburn on 4 or more of the 7 days before endoscopy were eligible to participate in this 4-week, randomized, double-blind, placebo-controlled trial. The absence of erosive esophagitis was established through endoscopy. Eligible patients were randomized to 1 of 3 treatment groups: omeprazole, 20 mg once daily; omeprazole, 10 mg once daily; or placebo. Patients were assessed at weeks 2 and 4. The efficacy of omeprazole for the treatment of heartburn was determined mainly through the following diary card data: daily resolution of heartburn and complete resolution of heartburn every day during 1 week of treatment. The efficacy of omeprazole for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea was also assessed. RESULTS: Of 359 randomized patients, 355 were included in the statistical analysis (intention-to-treat population). Daily proportions of patients with no heartburn were consistently greater in the 20-mg omeprazole group (62%, day 7; 74%, day 27) than in the 10-mg omeprazole group (41%, day 7; 49%, day 27) or the placebo group (14%, day 7; 23%; day 27). Complete resolution of heartburn every day during the last treatment week was significantly (P< or =.002) higher in the 20-mg omeprazole group (48%) than in the 10-mg omeprazole (27%) or placebo (5%) group. Omeprazole was significantly (P< or =.003) more effective than placebo for the treatment of acid regurgitation, dysphagia, epigastric pain, and nausea. CONCLUSIONS: Patients with symptomatic GERD require profound acid suppression to achieve symptomatic relief. Omeprazole, 20 mg once daily, was superior to omeprazole, 10 mg once daily, and to placebo in providing early and sustained resolution of heartburn, as well as treatment of other troublesome GERD symptoms.

Complete resolution of heartburn symptoms and health-related quality of life in patients with gastro-oesophageal reflux disease.

BACKGROUND: Medical treatments for gastro-oesophageal reflux disease (GERD) vary in their ability to completely resolve heartburn and other symptoms. Although GERD reduces health-related quality of life (HRQL) little is known about the relationship between resolution of heartburn symptoms with medical therapy and HRQL. We evaluated the association between complete resolution of heartburn symptoms and functioning and well-being in three samples of patients with GERD. METHODS: We analysed baseline and follow-up assessments of heartburn symptoms and HRQL scores from three clinical trials (total n=1351) comparing omeprazole and ranitidine for acute symptomatic treatment of GERD. Heartburn symptoms were measured using patient diaries and/or patient self-report. HRQL was assessed using the Psychological General Well-Being Index (PGWB) in all three clinical trials and the SF-36 Health Survey in two clinical trials. Resolution of heartburn symptoms was defined as no heartburn reported during the assessment period. RESULTS: We observed statistically significant differences favouring patients with no heartburn symptoms on the PGWB total score (P=0.018 to P < 0.0001) and anxiety (P=0.002 to P < 0.0001), general health (P=0.05 to P < 0. 0001), positive well-being (P=0.028 to P < 0.0001) and vitality (P=0. 05 to P < 0.0001) sub-scale scores at 4-14 weeks. Patients with no heartburn reported better SF-36 pain (P=0.005 to P < 0.0001) and general health perceptions (P=0.032 to P < 0.0001) compared with patients still experiencing heartburn symptoms at 4-24 weeks. SF-36 physical component summary scores were significantly better in patients with no heartburn symptoms compared with patients with heartburn symptoms at 4-24 weeks (P=0.013 to P=0.009), while mental component summary scores were only significantly different at 24 weeks (P=0.0005) in one of the two studies where the SF-36 was utilized. CONCLUSIONS: Complete resolution of heartburn symptoms was consistently associated with improvement in HRQL; the greatest impact was observed on measures of psychological well-being and physical functioning and well-being. Effective treatment of GERD that completely resolves heartburn results in clinically significant improvement in patient HRQL.

Efficacy of omeprazole versus ranitidine for symptomatic treatment of poorly responsive acid reflux disease-a prospective, controlled trial.

BACKGROUND: H2-receptor antagonists are widely used in patients with gastro-oesophageal reflux disease (GERD) and are frequently continued when symptoms persist. AIM: To compare the efficacy of omeprazole 20 mg once daily with that of ranitidine 150 mg twice daily in relieving GERD symptoms, in patients who remained symptomatic following a 6-week course of ranitidine therapy. METHODS: Patients with heartburn on at least 4 days/week but who did not have endoscopy to assess oesophageal mucosa could participate. This two-phase, prospective trial included a 6-week open-label phase (phase I), followed by an 8-week double-blind phase (phase II). Patients still symptomatic following treatment with ranitidine 150 mg twice daily (phase I) were randomized to double-blind treatment (phase II) with either omeprazole 20 mg once daily or ranitidine 150 mg twice daily. The primary efficacy variable was the proportion of patients with heartburn resolution during weeks 4 and 8 of phase II. RESULTS: Of the 533 patients with GERD who received ranitidine in phase I, 348 patients (65%) were still symptomatic. A total of 317 patients (59%) were randomized to double-blind treatment (phase II). At week 8, a significantly (P < 0.0004) greater proportion of omeprazole-treated patients (70%) experienced no more than mild heartburn compared with ranitidine-treated patients (49%). Complete resolution of heartburn also occurred in a significantly (P < 0. 00001) greater proportion of omeprazole-treated patients (46% vs. 16% of the ranitidine group at week 8). CONCLUSIONS: After 6 weeks of ranitidine treatment, the majority of patients with GERD were still experiencing moderate to severe heartburn. Omeprazole was significantly more effective than ranitidine in resolving heartburn in this group of patients.

High- versus standard-dose ranitidine for control of heartburn in poorly responsive acid reflux disease: a prospective, controlled trial.

OBJECTIVE: H2-receptor antagonists are commonly used as initial therapy in patients with gastroesophageal reflux disease (GERD) and are frequently continued at the same or higher doses when symptoms persist after 4-6 wk of therapy. Our objective was to compare the efficacy of twice-daily treatment with either ranitidine 150 mg b.i.d. or 300 mg b.i.d. in resolving heartburn in GERD patients who remained symptomatic after 6 wk of therapy with ranitidine 150 mg b.i.d. METHODS: This was a two-phase, prospective study. In the first phase, GERD patients with heartburn on > or = 4 of the 7 days before entry were treated with open-label ranitidine 150 mg b.i.d. for 6 wk. In the second phase, patients who were still symptomatic were randomized to 8 wk of double-blind ranitidine therapy at either the same (150 mg b.i.d.) or a higher dose (300 mg b.i.d.). The primary efficacy variable was the resolution of heartburn at wk 4 and 8, as monitored through diary cards. RESULTS: Of the 481 patients treated for 6 wk in phase I, 285 (59%) were still symptomatic; 271 patients (95% of those still symptomatic) were randomized to double-blind treatment with ranitidine. In phase II, 45% of the patients in each treatment group experienced no more than mild heartburn; complete heartburn resolution was observed in <20% of patients in either group at wk 4 and 8. There were no significant differences in efficacy between the two treatment groups. CONCLUSIONS: These results indicate that the majority of GERD patients still have symptoms of heartburn after 6 wk of ranitidine therapy. Only a minority of these patients experience complete relief of heartburn after an additional 8 wk of treatment, which demonstrates that doubling the dose of ranitidine is not efficacious.

Determining the cost of gastroesophageal reflux disease: a decision analytic model.

OBJECTIVE: To design a decision analytic model to help determine the costs associated with various treatment regimens for gastroesophageal reflux disease (GERD). STUDY DESIGN: A decision analytic model incorporating Markov processes was developed to calculate clinical and direct economic outcomes for patients with GERD after 2 years of treatment. PATIENTS AND METHODS: We used retrospective data in the Markov model to generate clinical and economic outcomes. The primary data sources were the 1993 MarketScan claims database, the 1992 National Hospital Discharge Survey, and the clinical literature. RESULTS: Patients with mild GERD (17.6% of patients) contributed 37.8% of costs, while those with moderate to severe disease (14.4% of patients) contributed 49.9% of costs. The remaining 12.3% of costs was spent on the 68% of patients with non-GERD diagnoses. The class of drugs with the highest acquisition cost--proton pump inhibitors--had the lowest total cost per case. The high level of efficacy of these drugs may explain this result. Sensitivity testing showed no evidence that our model's results depended heavily on any one probability or cost factor. CONCLUSIONS: This model showed that patients with moderate to severe GERD were the most expensive cases to treat and that proton pump inhibitors resulted in the lowest total cost per case. Further testing and manipulation of the model are required to gain a better understanding of the trade-offs involved in different options for GERD management.

Tongue necrosis due to vasculitis.

We describe a 7-year-old boy with necrosis of the tongue due to a generalized vasculitis, with symptoms and signs consistent with periarteritis nodosa and appearing after an infection with streptococci. Approximately one-third of the tongue had to be extirpated.

Cimetidine improves GERD symptoms in patients selected by a validated GERD questionnaire.

A questionnaire was constructed and validated to improve the accuracy of symptom assessment in diagnosing gastro-oesophageal reflux disease (GERD). The GERD questionnaire consisted of four questions describing an upward moving, uncomfortable feeling in the chest frequently accompanied by retrosternal burning that is improved with antacids. It was found that if a patient answered yes to all four questions the likelihood was 85% that erosive oesophagitis would be detected on endoscopy or that pathological gastro-oesophageal reflux on 24-hour pH-monitoring would be documented, or both. The GERD questionnaire was used to identify 269 patients with probable GERD who after one week on placebo entered a 2-week double-blind placebo-controlled study which was completed by 251 patients. Cimetidine (400 mg) b.d. was given to 124 patients and placebo to 127 patients. On diary cards the patients noted the number, the mean duration and the mean severity of GERD symptoms episodes. Cimetidine was significantly superior to placebo in increasing the percentage of symptom-free days, and in reducing the median number of daily symptom episodes. This trial demonstrates that 400 mg cimetidine b.d. is effective in improving GERD symptoms in patients identified by a descriptive, validated GERD questionnaire.

Outcome 5 years after 360 degree fundoplication for gastro-oesophageal reflux disease.

Forty patients with a mean age of 45 (range 22-65) years were operated on between 1982 and 1985 for gastro-oesophageal reflux disease with a short floppy 360 degree fundoplication. The results of the operation were determined by endoscopy, oesophageal manometry, ambulatory 24-h pH recording and symptom evaluation 6 months and 5 years after operation. These results were compared with findings in healthy controls. The median pressure in the lower oesophageal high-pressure zone was 13.3 (interquartile range (i.q.r.) 11.3-21.3) mmHg after 5 years, which did not differ significantly from the value at 6 months' follow-up or from that in controls. It was, however, significantly higher than the preoperative pressure. The median intra-abdominal length of the high-pressure zone was 1.7 (i.q.r. 1.3-2.3) cm after 5 years, significantly less than at 6 months but equal to control length. Measurement of the proportion of total time at pH < 4 at 5 years (median 0.2 (i.q.r. 0.0-0.6) per cent) and 6 months after operation revealed a significant reduction in acid reflux compared with preoperative values and normal controls. There was no significant difference in acid exposure between the two postoperative investigations. Endoscopy showed that 27 patients had no oesophagitis, three had erythema and three persistent Barrett's oesophagus 5 years after operation. Normal belching was possible in 22 patients and 18 experienced increased flatulence 5 years after fundoplication. An independent gastroenterologist found that the result was excellent in 16 patients, good in 16 and fair in four; two patients had a poor overall outcome of the operation. It is concluded that a 360 degree fundoplication provides good long-term control of reflux and that slight symptoms of overcompetence are common among patients operated on without affecting the overall result.

Heartburn--the acid test.

To determine whether symptoms of gastro-oesophageal reflux are related to the degree of oesophageal acid exposure, 190 patients (of 220 referred) with heartburn and acid regurgitation were compared with 50 normal subjects. A definite relationship between frequency of reflux symptoms and degree of oesophageal acid exposure was found both in patients with and without oesophagitis. We conclude that the frequency of gastro-oesophageal reflux symptoms is related to degree of oesophageal acid exposure.

Total gastrectomy and oesophagojejunostomy with linear stapling devices.

When performing total gastrectomy and oesophagojejunostomy with a circular stapling device two disadvantages are obvious; firstly, a purse-string suture is needed, and secondly the instrument can be extremely difficult to introduce if the oesophagus is narrow, so that the risk of rupture is substantial. We therefore developed the following technique. When the specimen is attached only to the oesophagus, and the Roux-en-Y loop has already been divided with a linear stapling device, a small incision is made on the back wall of the oesophagus and antimesenterically 6 cm distal to the cut end of the Roux-en-Y loop. The two forks of the GIA or the PLC 50 instrument are introduced into the oesophagus and jejunum, and the two organs are brought together at the hiatus. The instrument is closed and fired. The residual opening is closed with a linear stapler which also includes the front wall of the oesophagus. With a knife, the oesophagus and excessive amounts of tissue are trimmed away, and the oesophagojejunostomy is completed. Fifteen patients (median age 67 years) had a postoperative hospital stay of 10 days (range 8-45 days) after this operation. Leakage occurred in one patient and one patient died. The anastomosis took 12 min to perform (range 8-20 min). Three reoperations were needed: intestinal obstruction, leakage and a negative exploration. The median width of the oesophagojejunal anastomosis 6 months after operation was 32 mm (range 27-40 mm). Oesophagojejunostomy performed with two linear staplers allows a quick and reliable anastomosis independent of oesophageal lumen size and a time-consuming purse-string suture.

Determinants of gastro-oesophageal reflux and their inter-relationships.

Gastro-oesophageal reflux was measured by 24-h ambulatory oesophageal pH monitoring in 220 patients with symptoms suggestive of gastro-oesophageal reflux disease. By multiple regression analysis it was found that the pressure in the distal oesophageal high pressure zone, the presence of a hiatal hernia, the intra-abdominal length of the high pressure zone, the amplitude of the contraction waves in the distal oesophagus and age all significantly participated in the determination of the amount of gastro-oesophageal reflux. The pressure in the distal oesophageal high pressure zone was the single variable that correlated most strongly to the amount of reflux. Although the amount of reflux increased significantly with increasing weight as measured by Broca's index, this variable did not participate in the determination of reflux by the multiple regression test. The study emphasizes the role of the pressure and intra-abdominal length of the distal oesophageal high pressure zone as the primary antireflux barrier. It also shows that a hiatal hernia plays a role in generating gastro-oesophageal reflux through a mechanism other than affecting the pressure and the intra-abdominal length of the high pressure zone.

Alkaline phosphatase in cholestatic and cirrhotic rats. A biochemical and histochemical study.

Alkaline phosphatase (ALP) was studied by enzyme histochemical methods and by biochemical quantitations in rat livers with chronic bile duct obstruction and experimental cirrhosis. The most evident ALP increase was histochemically found in portal tracts of rats with bile duct obstruction and localized to the walls of proliferating blood vessels. Furthermore, a slight canalicular membrane enzyme increase was histochemically found in both groups, most evident in cirrhosis, whereas the biochemical assay of ALP in serum and liver from both pathological groups showed 3 times higher values compared to controls. The portal tracts did not seem to contribute to the serum increase, since the rise of serum ALP was similar in chronic bile duct obstruction and in experimental cirrhosis without changes of the portal tracts. It is concluded that the increase ALP activity in serum from rats with bile duct obstruction and cirrhosis mainly has a hepatocytic origin.

Bile salts in the esophagus of patients with esophagitis.

It is controversial whether bile salts are important in the pathogenesis of esophagitis. By sampling esophageal contents during ambulatory 24-h pH-monitoring we found that in a group of 18 patients with esophagitis all but 1 had detectable concentrations of bile salts in their esophagus. The concentrations of bile salts were low, however, and similar to those found in the gastric juice of 10 normal controls. It is concluded that bile salts are present in the esophagus of patients with esophagitis and that their presence results from duodenogastric reflux. The role of these refluxed bile salts in the pathogenesis of esophagitis is, however, unclear.

Reproducibility of ambulatory oesophageal pH monitoring.

To evaluate the reproducibility of ambulatory 24 hour intraoesophageal pH monitoring, 20 patients were randomly selected to undergo two consecutive investigations. Fifteen patients were classified as either abnormal, or normal on both test days. The amount of acid reflux, expressed as percentage of time with oesophageal pH below 4.0 during the two 24 hour periods, showed 77% concordance. The upright and recumbent periods of measurement showed different degrees of concordance: 83% and 62%, respectively. The reproducibility during time periods of different length was found to increase with increasing length of day time pH recording. A 16 hour period during evening and night had a reproducibility of only 58%, however. It is concluded that there is fairly good reproducibility when measuring gastro-oesophageal reflux over 24 hours, but that the reproducibility is poorer at night, during the postprandial period and when daytime monitoring is shorter than 10 hours.

Gastro-esophageal reflux disease.

'Gastro-esophageal reflux' is the passage of gastric content into the esophagus. Resulting typical symptoms are denoted as 'reflux like dyspepsia'. 'Reflux esophagitis' is the endoscopic or microscopic evidence of damage to the esophageal mucosa. Long-term intraesophageal pH-monitoring will establish 'pathologic gastroesophageal reflux' when 'acid exposure' time exceeds 5% of the monitoring time. GERD, 'gastro-esophageal reflux disease', is present when symptoms and/or esophagitis are caused by reflux. 'Columnar lined esophagus' is a better expression than 'Barret's esophagus'. Esophageal acid exposure increases during the day with a peak in the evening and little reflux after midnight. Treatment should probably be concentrated to evening time and not so much to night time.

Gastroesophageal reflux disease.

In these speculations of the future in gastro-esophageal reflux a hope is expressed that gastro-esophageal reflux disease is accepted as a separate entity. Treatment and diagnosis should not be confused with those of ulcer disease. Reflux disease is not a problem of too much acid in the stomach, but too much acid in the wrong place, the esophagus. The problem is mainly a leaking valve. Furthermore, the expression reflux like dyspepsia should be used when esophagitis or gastro-esophageal reflux disease is not established by endoscopy or pH-monitoring.

Ambulatory intraesophageal 24-hour pH-monitoring.

Changes in pH in the distal esophagus to detect reflux is the basis for ambulatory intraesophageal 24-hour pH-monitoring. Patients with symptoms that do not respond to therapy, patients with atypical symptoms and patients planned for antireflux surgery should undergo pH-monitoring. Pathologic reflux is detected by calculating acid exposure time. Information on the temporal relationship between reflux episodes and symptoms, and of the temporal pattern will also be obtained. The monitoring should be performed ambulatory during 24 hours. The patient should be as unrestricted as possible, except for acit food and beverages. Many types of equipment are available. Solid state memories are preferred, glass or antimony electrodes may be used and the data analysis should be performed on an ordinary personal computer.