Pain and quality of life in patients with symptomatic, non-complicated gallbladder stones: results of a randomized controlled trial.

BACKGROUND: Cholecystectomy is intended to relieve symptoms of gallstones, but unfortunately some patients will experience postcholecystectomy symptoms, including pain. There is limited information in the literature on gallstone-related pain and its influence on quality of life. The aim of this study was to examine how pain and quality of life in patients with symptomatic, uncomplicated gallbladder stones were affected by observation of their condition compared with removal of the gallbladder. METHODS: One-hundred and thirty-seven patients were randomized to observation (watchful waiting; n = 69) or cholecystectomy (n = 68) and answered questionnaires on pain, quality of life (PGWB index and NHP Part II) at randomization and fixed intervals (6, 12 and 60 months). All gallstone-related events (hospital admission for pain, complications of gallstone disease and cholecystectomy) and crossover between treatment groups were recorded. RESULTS: Of patients randomized to observation, 35 of 69 patients (51%) eventually underwent a cholecystectomy. Significant improvements in quality of life and pain scores were detected regardless of surgical treatment. Patients that subsequently experienced gallstone-related events had significantly higher pain scores at randomization than patients that did not experience any subsequent events, and this difference was maintained throughout follow-up. CONCLUSIONS: Unexpectedly, in the majority of patients symptoms did abate without any significant differences between groups in pain and quality of life. Patients that had high intensity and frequency of pain at randomization had a higher risk of experiencing subsequent events.

Symptomatic, non-complicated gallbladder stone disease. Operation or observation? A randomized clinical study.

BACKGROUND: Cholecystectomy has been recognized as the treatment of choice for symptomatic gallbladder stone disease. Not all patients are cured by an operation and the reason for having the gallbladder removed may rest on common practice rather than evidence-based medicine. The aim was to compare cholecystectomy with observation (watchful waiting) in patients with uncomplicated symptomatic GBS disease. Three-hundred-and-thirty-eight patients were considered for participation in the study; 45 patients were excluded according to predefined criteria and 156 did not join for other reasons. The remaining 137 were randomized to cholecystectomy (n = 68) or non-operative, expectant treatment (n = 69). METHODS: Randomized patients were contacted regularly and followed for a median of 67 months. All gallstone-related hospital contacts were registered in both randomized and excluded patients. RESULTS: Eight of the patients randomized to cholecystectomy did not undergo operation, while 35 of the patients randomized to observation later had their gallbladders removed. The cumulative risk of having a cholecystectomy seemed to level off after 4 years. Gallstone-related complications occurred in 3 patients in the observation group, 1 in the operation group and 5 of 201 excluded patients. After cholecystectomy, 16 of 222 patients had a major complication and 10 a minor. CONCLUSIONS: We found that non-operative expectant treatment carries a low risk of complications. Patients should be informed that watchful waiting is a safe option.

Piperacillin/tazobactam compared with cefuroxime/ metronidazole in the treatment of intra-abdominal infections.

OBJECTIVE: To assess the effect of piperacillin/tazobactam compared with cefuroxime/metronidazole in the treatment of patients with intra-abdominal infections. DESIGN: Randomised open study. SETTING: 16 Swedish and 6 Norwegian hospitals. SUBJECTS: 269 patients with intra-abdominal infections were randomised and treated with at least one dose of each study drug. 205 patients, 105 treated with piperacillin/tazobactam and 100 with cefuroxime, were clinically evaluable for follow up (had been given the full course of treatment). INTERVENTION: Patients were given piperacillin 4g/tazobactam 0.5 g every 8 hours or cefuroxime 1.5 g every 8 hours plus metronidazole 1.5 g every 24 hours. Each patient was to be treated for a minimum of 3 days and not more than 10 days. MAIN OUTCOME MEASURES: Clinical evaluation of infection at the end of and 4-6 weeks after treatment. Evaluation of safety and tolerance to the drugs and bacteriological susceptibility to the treatment drugs. RESULTS: In the intention to treat analysis treatment was equally successful for piperacillin/ tazobactam (103/140, 74%) and the cefuroxime/metronidazole groups (90/129, 70%) (p = 0.6). Corresponding figures for the clinically evaluable group were 102/105 (97%) and 94/100 (94%) for piperacillin/tazobactam and cefuroxime/metronidazole groups, respectively, at the end of treatment. At late follow up, 92/105 (88%) and 83/100 (83%) in the two groups, respectively, remained free of infection. The side effects of the treatment were mild and evenly distributed between the two groups. Most pathogens were susceptible to the drugs in both treatment groups. CONCLUSION: Both piperacillin/tazobactam and cefuroxime/metronidazole are well suited to the treatment of patients with intra-abdominal infections, and we found no significant difference between the two. The drugs were safe and well tolerated in the regimens used.

Development of play-the-winner design: weighting and accumulation of information.

BACKGROUND: Play-the-Winner (PTW) design was compared with Weighted-Play-the-Winner (WPW) design with regard to sensitivity to discriminate between treatments. METHODS: In total, 231 patients undergoing digestive surgery were included in a PTW study comparing safety of enoxaparin and dextran-70 in the prevention of venous thrombo-embolism. In the PTW model each patient was classified as a 'winner' or 'loser'. The treatment was changed when a patient was classified as 'loser', otherwise the same treatment was continued for the next patient. The study was performed by using a PTW design, but with all assessments needed for a WPW simulation. In the WPW design, a 'loser score' was calculated for each patient and summarized to a 'loser index' for consecutive patients given the same treatment. When this index exceeded a predefined value, treatment was changed and the 'loser index' set to zero. The WPW model with inheritance (WPWI) is identical to WPW, except that the overload of 'loser index' from the previous sequence with the same treatment was used as the starting value for the next. RESULTS: The PTW study revealed superiority of enoxaparin. This was enforced in the WPW model and further increased by WPWI. CONCLUSION: Changing from the PTW to WPW design and further to WPWI increased the sensitivity of the model, but at the same time the complexity of the design.

One-week omeprazole treatment in the diagnosis of gastro-oesophageal reflux disease.

BACKGROUND: Symptoms of gastro-oesophageal reflux are common, and currently available methods for diagnosing reflux disease are expensive and uncomfortable for the patient. The diagnostic value of a treatment test with omeprazole is unclear. METHODS: Patients with dyspepsia including heartburn admitted for upper gastrointestinal endoscopy were studied in a prospective, randomized, double-blind Scandinavian multicentre study. Before entry 188 patients were enrolled, and 160 were randomized to 1-week treatment with 20 mg omeprazole twice daily or placebo. Gastro-oesophageal reflux disease (GERD) was defined as reflux oesophagitis Savary-Miller grades II-III at endoscopy or pH < 4 exceeding 4% of the total time at 24-h oesophageal pH-monitoring and was found in 135 patients. The treatment test was considered positive when the patient's symptoms improved during the treatment week compared with the pretreatment day. RESULTS: The sensitivity in diagnosing reflux disease was 71-81% with omeprazole as a diagnostic test, compared with 36-47% for placebo during treatment days 3-7. The specificity was similar for the two treatment arms during the first days of the study. During the end of the week a larger proportion of the patients with normal endoscopy and pH test responded to omeprazole treatment, giving omeprazole lower specificity than placebo. The investigators' overall evaluation of whether the patient was a responder to the test had a sensitivity of 75% and a specificity of 55% in the omeprazole-treated patients. The corresponding figures in the placebo group were 17% and 92%, respectively. CONCLUSION: One week of omeprazole treatment is a simple diagnostic test with a fairly high sensitivity. The specificity is poor owing to the placebo effect and to the lack of a gold standard in diagnosing reflux disease.

Ranitidine effervescent and famotidine wafer in the relief of episodic symptoms of gastro-oesophageal reflux disease.

BACKGROUND: The aim of this study was to measure the efficacy of 150-mg ranitidine effervescent tablets compared with 20-mg famotidine wafers in the management of patients presenting to primary care physicians with episodic symptoms of gastro-oesophageal reflux disease (GORD). METHODS: The study was of a multicentre, open, randomized, parallel-group design in which 32 Norwegian general practitioners participated. After a pre-treatment demographic and symptom assessment, eligible patients were allocated to either ranitidine effervescent tablet or famotidine wafer. Patients were then provided with the study medication, a stopwatch, and a 2-week symptom diary card. Efficacy was primarily determined by the time to adequate symptom relief for the first symptom episode. RESULTS: In total, 377 patients were recruited to the study; 187 patients received ranitidine effervescent, and 190 received famotidine wafer. More than 50% of the patients had daily GORD symptoms before recruitment. Median time to adequate symptom relief was 15 min in the ranitidine group and 18.5 min in the famotidine group (P = 0.005). Adequate symptom relief within 60 min was reported by 165 (92%) ranitidine patients and 156 (84%) famotidine patients (P = 0.02). The number of non-responders after 60 min was twice as great in the famotidine group: 30 (16%) versus 15 (8%). A greater proportion of patients in the famotidine group liked taking the wafer formulation: 173 (94%) versus 126 (70%) (P = 0.001). CONCLUSION: There was a statistically significant difference in favour of 150-mg ranitidine effervescent tablets in terms of time to adequate symptom relief and the proportion of patients who achieved adequate symptom relief for the first episode. A greater proportion of patients in the famotidine group liked the type of formulation than in the ranitidine group.

Randomization to surgery or observation in patients with symptomatic gallbladder stone disease. The problem of evidence-based medicine in clinical practice.

BACKGROUND: The description and understanding of gallbladder stone disease in the medical literature are difficult because an assessment of the natural course of this symptomatic disease, with separation of patients in strictly defined groups, is generally lacking. METHOD: A multicenter study was carried out with patients randomized to either surgery or conservative, expectant treatment to examine optimal treatment and natural history in well-defined groups of symptomatic gallbladder stone disease with pain, episodes only (study group 1) or acute cholecystitis (study group 2). The patients were between 18 and 80 years of age and had right upper quadrant or midline epigastric pain and ultrasonographic evidence of gallbladder stone, with or without acute cholecystitis. Medical treatment was ordinated on the basis of signs and symptom severity. Patients randomized to surgery were placed on the hospital's waiting list and electively operated on with cholecystectomy as soon as conveniently possible. Preliminary results of follow-up are based on questionnaires mailed at regular intervals and consultations if required by the patients' symptoms. Quality of life and freedom from pain are study end points for evaluation. RESULTS: Five hundred and one patients were considered for the study, 318 patients (63.5%) belonging to group 1 and 183 (36.5%) to group 2. One hundred and eighty-four patients (36.7%) were randomized, 120 (24%) in group 1 and 64 (12.7%) in group 2. Three hundred and seventeen patients (63.3%), with an equal proportion from each study group, were excluded, the largest number of patients because of incapacitating pain or serious presenting symptoms (26%). More women (81%) than men (19%) had pain alone (group 1), but the sex ratio was reduced, 56% women and 44% men, in patients with acute cholecystitis (group 2), with a highly significant difference (P = < 0.001) between the two groups. A significant difference in patient withdrawal from randomized treatment was registered, with 24% from observation and 12% from surgery (P = 0.032), but with an equal distribution in the two study groups. CONCLUSIONS: A randomized trial of this nature is feasible but extremely difficult to perform because of the heterogeneous nature of gallbladder stone disease, leading to exclusion of many patients and difficulties in measuring and evaluating outcome variables.

Preoperative local infiltration with ropivacaine for postoperative pain relief after inguinal hernia repair. A randomised controlled trial.

OBJECTIVE: To assess the effect of preoperative local anaesthesia with ropivacaine and find out if there was a dose-response relationship with postoperative pain after inguinal hernia repair. DESIGN: Randomised, double-blind, placebo-controlled trial. SETTING: Two Swedish and two Norwegian hospitals. SUBJECTS: 131 Male patients undergoing elective inguinal hernia repair. INTERVENTION: Infiltration of the inguinal field before operation with 0.5% ropivacaine 40 ml (200 mg), 0.25% ropivacaine 40 ml (100 mg) or saline 40 ml. MAIN OUTCOME MEASURES: Wound pain at rest and during mobilisation, pressure exerted to reach pain threshold and maximum pain tolerance after 3, 6, 10, and 24 hours, and after 7 days; consumption of analgesics; and Quality of Life assessed by two independent questionnaires before and after operation. RESULTS: Pain scores after 3 hours were significantly lower in the ropivacaine groups compared with the saline group for all variables (p < 0.05). At 6 hours pain scores were significantly lower for ropivacaine 0.5% compared with saline for wound pain during mobilisation and pressure exerted to reach maximum pain tolerance. Patients given saline made their first request for analgesics significantly sooner than in the other two groups (p < 0.05), and a significantly larger percentage of them requested analgesics during the first 24 hours (p < 0.05). Evaluation of the Quality of Life questionnaires showed no significant differences between the groups. CONCLUSION: Ropivacaine has a significant, dose-related pain-reducing effect in the immediate postoperative period but we could find no support for the theory that preoperative infiltration analgesia reduces long term pain.

Prolonged thromboprophylaxis following hip replacement surgery--results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin)

Discontinuation of thromboprophylaxis a few days after surgery may unmask delayed hypercoagulability and contribute to late formation of deep venous thrombosis (DVT). To investigate whether thromboprophylaxis should be prolonged beyond the hospital stay, a prospective, double-blind randomised study was conducted in 308 patients. All patients received initial thromboprophylaxis with dalteparin, dextran and graded elastic stockings. On day 7, patients were randomised to receive dalteparin (Fragmin) 5000 i.u. once daily, or placebo, for 4 weeks. All patients were subjected to bilateral venography, perfusion ventilation scintigraphy and chest X-ray on days 7 and 35. Patients with venographically verified proximal DVT on day 7 were withdrawn from the randomised study to receive anticoagulant treatment. The overall prevalence of DVT on day 7 was 15.9%. On day 35, the prevalence of DVT was 31.7% in placebo-treated patients compared with 19.3% in dalteparin-treated patients (p = 0.034). The incidence of DVT from day 7 to day 35 was 25.8% in the placebo-treated group versus 11.8% in the dalteparin-treated group (p = 0.017). The incidence of symptomatic pulmonary embolism (PE) from day 7 to day 35 was 2.8% in the placebo-treated group compared with zero in the dalteparin-treated group. This included one patient who died from PE. No patients experienced serious complications related to the injections of dalteparin or placebo. This study shows that prolonged thromboprophylaxis with dalteparin. 5000 IU, once daily for 35 days significantly reduces the frequency of DVT and should be recommended for 5 weeks after hip replacement surgery.

[Lack of specialists in gastroenterological surgery]. / Spesialistmangel innen gastroenterologisk kirurgi.

Despite the fact that a prognosis in 1991 predicted a surplus of ten gastroenterological surgeons in 1994, several hospitals are now experiencing a lack of applicants. In order to define the scope of this problem, the Norwegian Gastroenterological Society and The Specialty Committee for Gastroenterological Surgery sent a questionnaire and made a telephone query to all Norwegian Surgical Departments in autumn 1995. There were 21 vacant posts and 27 specialists are still needed to carry out the tasks the hospitals are instructed to perform. An initiative must be taken to increase the capacity and geographical distribution of the education and improve the working conditions, and thereby job satisfaction, of gastroenterological surgeons.

[Bilateral intra-patellar tendon rupture in a previously healthy woman]. / Bilateral infrapatellar seneruptur hos tidligere frisk kvinne.

Bilateral infrapatellar tendon rupture is a relatively rare injury. We describe the case of a 32 year old woman who stumbled and sustained a bilateral infrapatellar tendon rupture while jogging. In our opinion, this represents an unusual mechanism of injury, and we also find it unusual that it was a bilateral injury in an otherwise healthy patient. Diagnosis was confirmed by surgical exploration eight days after admission to hospital. Despite repeated clinical, X-ray and ultrasound examinations, the diagnosis was delayed since we initially did not consider the trauma adequate to cause such an extensive injury. The diagnosis of patella tendon rupture should be based on careful consideration of the history of the injury and thorough clinical examination. X-ray and ultrasound can be of diagnostic help.

Prophylaxis of venographically diagnosed deep vein thrombosis in gastrointestinal surgery. Multicentre trials 20 mg and 40 mg enoxaparin versus dextran.

OBJECTIVE: To compare enoxaparin and dextran 70 for the prophylaxis of venographically diagnosed deep vein thrombosis (DVT) after gastrointestinal operations. DESIGN: Part 1: randomised double blind trial; Part 2: single blind study with historical controls. SETTING: Eight Norwegian hospitals. SUBJECTS: 381 Patients undergoing elective gastrointestinal operations. INTERVENTIONS: Part 1 (n = 329): enoxaparin 20 mg subcutaneously starting two hours before operation and continuing until the patient was fully mobilised or had had 10 injections and a placebo infusion of 0.9% sodium chloride, or dextran 70,500 ml at the start of the operation, on the evening of operation, and on the first, third, and fifth postoperative days and placebo subcutaneous injections. Part 2 (n = 52): enoxaparin 40 mg in the same regimen as part 1 (compared with 39 historical controls). Venograms 4-6 days post-operatively. MAIN OUTCOME MEASURE: Venographically confirmed DVT. RESULTS: Part 1: Because of the high overall incidence of DVT an interim analysis was done which showed 33/101 DVT (33%) among high risk patients in the enoxaparin 20 mg group and 33/107 (31%) in the dextran 70 group. The corresponding figures for patients at medium risk were 2/27 (7%) for enoxaparin 20 mg and 5/27 (19%) for dextran 70 (95% confidence interval (CI) for the difference--11.9 to 9.8). Part 2: the dose of enoxaparin was therefore increased to 40 mg and prophylaxis restricted to patients with cancer. There were 6/49 DVT (12%), which was compared with a random sample from the dextran 70 group from part 1 (historical controls) in which the incidence was 15/39 (38%, 95% CI of the difference 4.0 to 8.4). There were no pulmonary emboli, only 4 thrombi were above the knee and there were 4, 1 and 3 clinical DVT in the 20 mg and 40 mg enoxaparin, and dextran 70 groups, respectively. CONCLUSIONS: Enoxaparin 20 mg and dextran 70 are effective prophylaxis for patients at medium risk, but enoxaparin 40 mg is required for those at high risk.

The effect of cisapride and ranitidine as monotherapies and in combination in the treatment of uncomplicated gastric ulceration.

BACKGROUND: Stimulation of gastric motility has been supposed to accelerate the healing of gastric ulcer. The combination of the prokinetic drug cisapride and the H2 blocker ranitidine was tested in the treatment of uncomplicated gastric ulcer. METHODS: Cisapride, 20 mg twice daily (Cis), and ranitidine, 150 mg twice daily (Ran), were given as monotherapies and in the combination 20 mg cisapride and 150 mg ranitidine daily (Cis + Ran) for a maximum of 8 weeks. The study was multicentre, randomized, and double-blind. RESULTS: A total of 197 patients were included. Healing rates in the per-protocol analysis after 4 and 8 weeks' treatment were 61%/84%, 52%/69%, and 61%/92% for the Cis + Ran (n = 56), Cis (n = 58), and Ran (n = 59) treatment groups. No statistically significant difference in healing rates was seen when comparing Cis + Ran with the monotherapies. Symptom relief at the end of treatment was significantly better in the Ran group than in the Cis + Ran group with regard to epigastric pain (p = 0.01) and vomiting (p = 0.05). Patients' global evaluation of treatment was in favour of Ran in comparison with Cis + Ran treatment (p = 0.04). CONCLUSIONS: Combination of cisapride and ranitidine in the treatment of gastric ulcer did not enhance the healing rate or improve symptom relief in patients treated for uncomplicated gastric ulcer when compared with the monotherapies.

[Extirpation of benign renal cysts with laparoscopic technique]. / Ekstirpasjon av benign nyrecyste med bruk av laparoskopisk teknikk.

Laparoscopic surgery is rapidly increasing its field of application. We describe the uncomplicated use of peritoneoscopic techniques to remove a benign renal cyst. No previous report of this mini-invasive, patient-friendly and cost-effective method has been found in the literature. It should be considered in the rare cases where surgery is indicated as treatment for this benign condition.

Two and four weeks' treatment for duodenal ulcer. Symptom relief and clinical remission comparing omeprazole and ranitidine. Scandinavian Clinics for United Research.

In a Swedish-Norwegian multicentre study patients with endoscopically verified duodenal ulcers (greater than 5 mm) were randomized to 2 or 4 weeks of treatment with either 20 mg omeprazole once daily or 300 mg ranitidine once daily. The aim was to evaluate 2 and 4 weeks' treatment with regard to symptomatic improvement during treatment, relapse after treatment, and safety of the two drugs. Endoscopy was not performed to check healing at the end of treatment. Instead the patients were instructed to contact the investigator in the event of recurrence of symptoms for renewed endoscopy. Follow-up was ended 10 weeks after stopping active treatment. Altogether 450 patients were evaluated at 17 centres. The symptomatic improvement during treatment was good in all groups, with significantly better reductions of daytime pain and heartburn in omeprazole-treated patients. Symptomatic relapse was commonest in the 2-week ranitidine group (57%), significantly more than in the 2-week omeprazole group (31%) (p less than 0.003). In the 4-week groups relapse rates were 34% (ranitidine) and 39% (omeprazole) (NS). It is suggested that in the short-term treatment of acute duodenal ulcer 20 mg omeprazole once daily is most rationally used in a 2- to 4-week regimen, whereas 300 mg ranitidine once daily should not be used for less than 4 weeks.

[Common bile duct calculi after biliary surgery. Postoperative endoscopic papillotomy is the solution]. / Stein i ductus choledochus etter galleoperasjon. Postoperativ endoskopisk papillotomi løser problemet.

In 37 patients with retained bile duct stones after operation using a T-tube, endoscopic papillotomy (EPT) was used as the therapeutic procedure. In 27 patients the stones were successfully removed in one session. Eight patients needed two to six endoscopic attempts before the stones could be removed. In two patients we failed to solve the problem endoscopically; in both patients we could remove the stone through the T-tube channel using a Dormia basket. The endoscopic method of removing retained bile duct stones is safe and quick. Most of the patients can be discharged from the hospital the following day.

Recurrent ulcer after treatment with cimetidine or sucralfate.

The recurrence of peptic ulcer disease after successful treatment with 400 mg cimetidine twice daily or 1 g sucralfate four times daily was investigated in a double-blind, 1-year follow-up study. Endoscopy was performed if ulcer symptoms recurred and 2-4 and 9-11 months after endoscopically confirmed healing of the initial ulcer. No anti-ulcer medication was permitted during the follow-up period. The recurrence rates were 71% in the cimetidine group (n = 143) and 68% in the sucralfate group (n = 115) (p greater than 0.3). The rate of asymptomatic ulcer relapse was 26% in the cimetidine and 23% in the sucralfate group (p greater than 0.4). The time to relapse did not differ between the treatment groups (p greater than 0.3). In the cimetidine group smokers had a higher 12-month recurrence rate than non-smokers, 83% compared with 58% (p less than 0.01). The corresponding figures in the sucralfate group were 76% and 57% (p = 0.057). The median time to recurrence in the cimetidine-treated group was 17 weeks among smokers, compared to 43 weeks among non-smokers (p less than 0.001). In the sucralfate-treated group the median time to recurrence was 23 weeks among smokers and 32 weeks among non-smokers (p greater than 0.3). Pre-study use of non-steroidal anti-inflammatory drugs and the time to healing of the initial ulcer did not influence the relapse rates in either of the treatment groups.

Relapse rate of healed duodenal, prepyloric, and gastric ulcers treated either with sucralfate or cimetidine.

A multicenter double-blind study was designed to compare the relapse rates of peptic ulcers after initial healing with a cytoprotective agent and a histamine (H2)-receptor antagonist. Patients with endoscopically verified prepyloric or duodenal ulcers were treated with cimetidine 400 mg twice daily or sucralfate 1 g four times daily for a maximum of eight weeks; gastric ulcers were treated for up to 12 weeks. Patients with healed ulcers were followed up to 12 months, during which time anti-ulcer medication was not permitted. Control endoscopy was performed two to four and nine to 11 months after healing and at the time of symptomatic relapse. A total of 258 patients were followed for 12 months; of these, 143 had been previously treated with cimetidine and 115 had been treated with sucralfate. The relapse rates and the median time to relapse did not differ between the two groups. After 12 months, 71 percent of the previously cimetidine-treated patients and 68 percent of the sucralfate-treated patients had experienced a relapse. Smoking significantly increased the relapse rate and shortened the time to relapse in the total study population and among cimetidine-treated patients; it had no such effect in the sucralfate-treated group.