Nadolol plus isosorbide mononitrate compared with sclerotherapy for the prevention of variceal rebleeding

BACKGROUND: Patients who have bleeding from esophageal varices are at high risk for rebleeding and death. We compared the efficacy and safety of endoscopic sclerotherapy with the efficacy and safety of nadolol plus isosorbide mononitrate for the prevention of variceal rebleeding. METHODS: Eighty-six hospitalized patients with cirrhosis and bleeding from esophageal varices diagnosed by endoscopy were randomly assigned to treatment with repeated sclerotherapy (43 patients) or nadolol plus isosorbide-5-mononitrate (43 patients). The primary outcomes were rebleeding, death, and complications. The hepatic venous pressure gradient was measured at base line and after three months. RESULTS: Base-line data were similar in the two groups, and the median follow-up was 18 months in both. Eleven patients in the medication group and 23 in the sclerotherapy group had rebleeding. The actuarial probability of remaining free of rebleeding was higher in the medication group for all episodes related to portal hypertension (P = 0.001) and variceal rebleeding (P = 0.002). Four patients in the medication group and nine in the sclerotherapy group died (P = 0.07 for the difference in the actuarial probability of survival). Seven patients in the medication group and 16 in the sclerotherapy group had treatment-related complications (P = 0.03). Thirty-one patients in the medication group underwent two hemodynamic studies; 1 of the 13 patients with more than a 20 percent decrease in the hepatic venous pressure gradient had rebleeding, as compared with 8 of the 18 with smaller decreases in the pressure gradient (P = 0.04) for the actuarial probability of rebleeding at two years). CONCLUSIONS: As compared with sclerotherapy, nadolol plus isosorbide mononitrate significantly decreased the risk of rebleeding from esophageal varices.     

Sclerotherapy versus ligation in hemorrhage caused by rupture of esophageal varices. Direct meta-analysis of randomized trials

OBJECTIVES: To compare the advantages of endoscopic ligation and endoscopic sclerotherapy for bleeding esophageal varices, published randomized clinical trials were critically reviewed by meta-analysis. Only ten clinical trials concerning a history of recent or active bleeding esophageal varices were included. METHODS: The methodology, population, treatment and outcomes of each relevant trial were evaluated by duplicate independent review. RESULTS: Endoscopic sclerotherapy compared to banding ligation significantly increased the rate of rebleeding (OR: 1.6; 95% IC: 1.1-2.3) without increasing early mortality compared to endoscopic banding ligation (OR: 1.3; 95% IC: 0.8-1.9). The rate of varice eradication associated with these two types of treatment was not different (OR: 0.9; 95% IC: 0.6-1.3) but was obtained more quickly with endoscopic banding ligation (3.8 +/- 1.6 versus 5.8 +/- 2.2; P < 0.05). The rate of complications was higher after sclerotherapy (OR: 2.5; 95% IC: 1.7-3.7), in those cases with a positive heterogeneity test. CONCLUSIONS: This meta-analysis shows a lower morbidity with endoscopic banding ligation in patients with variceal hemorrhage. The most important advantage of endoscopic banding ligation was the reduction of the rate of rebleeding.     

Medical prophylaxis of haemorrhage from oesophageal varices in patients with liver cirrhosis

Haemorrhage from oesophageal varices is a life-threatening event in patients with liver cirrhosis. About 40-80% of patients surviving the first bleeding suffer a recurrence within 1 year. This high recurrence rate substantially contributes to the mortality in patients with liver cirrhosis. Therefore, various treatment regimens in both primary and secondary prophylaxis were studied. Most experience in medical primary prophylaxis was collected with beta-blockers, mainly propranolol. Treating patients with oesophageal varices with propranolol significantly reduces the incidence of first variceal bleeding. However, the effect on mortality is marginal, and primary prophylaxis is generally not recommended in these patients. Several studies support the hypothesis that medical prophylaxis with beta-blockers is more effective in reducing the rate of first oesophageal bleeding in patients with a high risk of haemorrhage, such as those with very large varices with red spots. A score to assess an individual patient's risk of variceal bleeding would be helpful, but until such a score has been validated, no general rule for this treatment decision can be given. In secondary prophylaxis, both beta-blockers and endoscopic therapy (sclerotherapy or ligation of the varices) are effective in lowering the rate of rebleeding. However, the effect on mortality was not significant in most studies. Several studies comparing the efficacy of medical prophylaxis and endoscopic treatment showed advantages of the endoscopic therapy with a greater reduction in recurrent bleeding episodes. However, medical prophylaxis with beta-blockers has the important advantage of being immediately effective, whereas endoscopic procedures provide the best protection against recurrent bleeding after complete obliteration of the varices. Therefore, in the first weeks and months of endoscopic therapy, additional treatment with beta-blockers may further reduce the risk of rebleeding. Only half of all studies on this topic reported a significant advantage with this combined therapy. Therefore, it seems reasonable to restrict this approach to patients with a high risk of rebleeding, such as patients with large sclerotherapy-derived oesophageal ulcers.     

Mesocaval interposition shunting in the treatment of bleeding oesophageal varices

OBJECTIVE: To assess the longterm results of mesocaval interposition shunt in the treatment of bleeding oesophageal varices. DESIGN: Retrospective study. SETTING: University hospital, Sweden. SUBJECTS: 60 patients with bleeding oesophageal varices in all Child's classes. 20 of whom were operated on as emergencies, and 40 as elective cases. INTERVENTIONS: A 14 mm polytetrafluoroethylene graft was used as an interposition shunt between the superior mesenteric vein and the vena cava. MAIN OUTCOME MEASURES: Rebleeding rate, portal blood flow, hepatic encephalopathy, morbidity, mortality, and survival. RESULTS: Rebleeding was rare and occurred mainly during the first 4 months after operation, (n = 5) in 10% of the patients, and at the 24 month follow-up, (n = 4) in 11% of the patients. Portal flow was measured preoperatively in 33 patients and in 22 (67%) it was hepatopetal. During follow-up it was reversed and after 24 months no patient had hepatopetal flow. Hepatic encephalopathy was present in 18 patients (20%) during follow-up. Shunts thrombosed in 9 patients (15%), 8 of which required reoperation. There was no operative mortality, but 4 patients (7%) died within 30 days of surgery. The main late cause of death (18/26) was liver failure. The 1 year survival was 80%, the 3 year survival 70% and the 5 year survival 60%. CONCLUSIONS: The mesocaval interposition shunt gives good longterm results and can be recommended both as an emergency and an elective procedure for patients with portal hypertension and bleeding oesophageal varices that are unresponsive to sclerotherapy.     

Better prevention of complications in the practice of sclerotherapy

Certain precautions are fundamental to the practice of sclerotherapy. The practitioner must make sure that the needle is well-positioned, and that the catheterized vein is, indeed, the varix he intends to inject; he should inject slowly and flexibly, always responding to the patient's slightest reaction. But quite apart from these basic precautions, the doctor must be physically and mentally prepared to carry out sclerotherapy. In particular, he must resist all temptations to try and do more than he is able: presumption and over-hastiness are risk-factors which should not be ignored.     

Prospective study of bacteremia rate after elastic band ligation and sclerotherapy of esophageal varices in patients with hepatosplenic schistosomiasis

Bone scintigraphy was performed in a 69-year-old male patient with adult T-cell leukemia suffering from right lower limb pain. Numerous sites of increased uptake were seen in the skull, left clavicle, bilateral humeri, bilateral radii and right femur and tibia. Bone radiographs showed multiple osteolytic lesions, most of which corresponded to the abnormal deposits on the bone scans with 740 MBq of 99mTc-hydroxymethylene diphosphonate. This pattern is rarely reported, but bone involvement of adult T-cell leukemia is not uncommon. Bone involvement was remarkable on the appendicular skeleton when compared with common metastatic bone tumors. Bone scintigraphy may be useful in detecting bone involvement in adult T-cell leukemia.     

Effects of cilazapril on renal haemodynamics and function in hypertensive patients: a randomised controlled study versus hydrochlorothiazide

In this study the efficacy and safety of short-term cilazapril administration on renal haemodynamics were evaluated in mild to moderate hypertensive subjects. Our final goal was to evaluate whether the reduction in blood pressure achieved by treatment was associated with maintained renal function. After a run-in period with placebo, 40 hypertensive subjects without renal or cardiac diseases were randomly allocated to a double-blind 4 week controlled trial with cilazapril 5 mg once a day (20 patients) or hydrochlorothiazide 25 mg once a day (20 patients). Renal haemodynamics measurements included effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) by radionuclide study using 131I-hippuran and 99mTc, according to the methods described by Schlegel and Gates, respectively. Effective renal blood flow [ERBF = ERPF/(1-Ht)], filtration fraction (FF = GFR/ERPF) and renal vascular resistance (RVR = MBP x 80/ERBF) were calculated. At the end of cilazapril and hydrochlorothiazide administration significant decreases (p < 0.001) in SBP, DBP and MBP vs baseline values were observed. In the cilazapril group a significant decrease (p < 0.001) in RVR and FF and a significant increase (p < 0.001) in ERPF and ERBF were also found. In the hydrochlorothiazide group a significant decrease (p < 0.001) in RVR was found. No important side effects were observed with either treatment. In conclusion our data indicate that both cilazapril and hydrochlorothiazide reduced blood pressure equally well but only cilazapril improved renal blood flow and reduced filtration fraction.     

A randomised multicentre study of human milk versus formula and later development in preterm infants

Whether breast milk influences later neurodevelopment has been explored in non-randomised studies, potentially confounded by social and demographic differences between feed groups. Here in a strictly randomised prospective multicentre trial, Bayley psychomotor and mental development indices (PDI and MDI) were assessed at 18 months postterm in survivors of 502 preterm infants assigned to receive, during their early weeks, mature donor breast milk or a preterm formula. These diets were compared as sole enteral feeds or as supplements to the mother's expressed breast milk. No differences in outcome at 18 months were seen between the two diet groups despite the low nutrient content of donor milk in relation to the preterm formula and to the estimated needs of preterm infants. These results contrast with those reported from our parallel two centre study that compared infants randomly assigned a standard term formula or the preterm formula during their early weeks; those fed standard formula, now regarded as nutritionally insufficient for preterm infants, were substantially disadvantaged in PDI and MDI at 18 months post-term. It is shown here that infants from that study fed solely on standard formula had significantly lower developmental scores at 18 months than those fed on donor breast milk in the present study; yet the standard formula had a higher nutrient content than the donor milk. Thus, donor milk feeding was associated with advantages for later development that may have offset any potentially deleterious effects of its low nutrient content for preterm infants. As these outcome advantages were not confounded by the social and educational biases usually associated with mothers' choice to breast feed, our data add significant support to the view that breast milk promotes neurodevelopment.     

Biofeedback training in treatment of childhood constipation: a randomised controlled study

BACKGROUND: Because abnormal defaecation dynamics, which can be modified by biofeedback, are considered to be the underlying problem in constipation, biofeedback training may be a useful treatment for constipation. This treatment has mainly been studied in uncontrolled trials. We evaluated defaecation dynamics and clinical outcome in chronically constipated children in a randomised study comparing conventional treatment and conventional treatment with biofeedback training. METHODS: Patients, 5 to 16 years old, were referred to the Academic Medical Center in Amsterdam by general practitioners, school doctors, paediatricians, and psychiatrists. They had to fulfil at least two of four criteria for paediatric constipation and were included if they had been treated medically for at least one month before randomisation. Patients had a medical history, abdominal and rectal examination, and anorectal manometry at the start and end of the 6-week intervention period. The conventional group received laxative treatment with additional dietary advice, toilet training, and maintenance of a diary of bowel habits. The biofeedback group received the same conventional treatment and additionally five biofeedback training sessions. During the first 3 weeks, patients visited the outpatient clinic weekly; two subsequent visits were twice monthly. FINDINGS: 94 patients were randomised to conventional treatment (CT) and 98 to conventional treatment with additional biofeedback training (CT+BF). Normal defaecation dynamics increased in the CT group from 41% to 52% (not significant) and in the CT+BF group from 38% to 86% (p = 0.001). At 6 weeks, more patients in the CT+BF group showed normal defaecation dynamics, compared to the CT group (p < 0.001). This result was unaltered by controlling for baseline status in a logistic regression model. At 1 year, successful treatment (defaecation frequency > or = 3/week, soiling and/or encopresis < 2/month, and no laxatives) was accomplished in 59% of the CT and 50% of the CT+BF group (p = 0.24). The results were maintained after 1 1/2 years follow-up. No association was found between achievement of normal defaecation dynamics and clinical outcome. INTERPRETATION: Additional biofeedback training compared to conventional therapy did not result in higher success rates in chronically constipated children. Furthermore, achievement of normal defaecation dynamics was not associated with success: abnormal defaecation dynamics seem not to play a crucial role in the pathogenesis of childhood constipation. Intensive conventional laxative treatment should remain the first choice in chronically constipated children.     

Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis

OBJECTIVE: To study the incidence of late deep venous thrombosis (DVT), and to evaluate a regimen of prolonged thromboprophylaxis after general surgery. DESIGN: Randomised, controlled, open trial, with blinded evaluation. SETTING: University hospital, Denmark. SUBJECTS: 176 consecutive patients undergoing major elective abdominal or non-cardiac thoracic operations, of whom 118 were eligible for evaluation. INTERVENTIONS: Thromboprophylaxis with a low-molecular-weight heparin, tinzaparin, given for four weeks (n = 58), compared with one week (control group, n = 60). MAIN OUTCOME MEASURES: Presence of DVT established by bilateral venography four weeks after the operation. RESULTS: The incidence of late DVT in the control group was 6/60 (10%, 95% confidence interval (CI) 4% to 21%). In the prophylaxis group it was 3/58 (5.2%, 95% CI 1% to 14%) (p = 0.49). CONCLUSION: Prolonged thromboprophylaxis had no significant effect on the incidence of DVT occurring late after general surgery.     

Popularity of less frequent follow up for breast cancer in randomised study: initial findings from the hotline study

OBJECTIVE: To compare the experiences of patients with breast cancer who were conventionally monitored with those in whom routine follow up was restricted to the time of mammography. DESIGN: Randomisation to conventional schedule of clinic visits or to visits only after mammography. Both cohorts received identical mammography and were invited to telephone for immediate appointments if they detected symptoms. SETTING: Combined breast clinic, Chelsea and Westminster Hospital. SUBJECTS: 211 eligible outpatients with a history of breast cancer. MAIN OUTCOME MEASURES: Acceptability of randomisation, interim use of telephone and general practitioner, satisfaction with allocation to follow up. RESULTS: Of 211 eligible patients, 196 (93%) opted for randomisation in the study. Of these, 55 were under 50 years, 78 were diagnosed fewer than five years before, 90 had stage T2-4 tumours, and 71 had involved axillary nodes. Patients who did not participate were more likely to be under 50 years, to be two to five years after diagnosis, and to have had aggressive primary disease. Twice as many patients in both groups expressed a preference for reducing rather than increasing follow up. No increased use of local practitioner services or telephone triage was apparent in the cohort randomised to less frequent follow up by specialists. CONCLUSIONS: Reducing the frequency of routine follow up has so far proved popular among patients with breast cancer at standard risk in this cohort. A multicentre study is needed to determine the effectiveness and cost-effectiveness of routine follow up with respect to disease outcomes.     

Early intervention and prevention in schizophrenia--experiences from a study in Stavanger, Norway

The paper gives an overview of current literature and research that makes the foundation and rationale for early intervention in functional psychosis, i.e. schizophrenia. The duration of untreated psychosis (DUP) and its practical implications are demonstrated. An outline of the prerequisites of the psychiatric services and the societal preconditions for effective early intervention strategies is given. The development of working clinical treatment programmes within the county of Rogaland, Norway, is described, as well as strategies towards enhancing the knowledge of serious psychiatric disorders among the population and thus making the foundation for effective and early help-seeking. The different resistance factors in relation to early intervention are introduced. Preliminary results of an early intervention is presented, indicating that it is possible to shorten DUP (from 114 to 20 weeks), and showing that DUP is the single most important predictor for poor prognosis.     

Endoscopic sclerotherapy versus variceal ligation in the long-term management of patients with cirrhosis after variceal bleeding. A prospective randomized study

BACKGROUND/AIMS: Long-term endoscopic injection sclerotherapy of oesophageal varices prevents rebleeding in patients with cirrhosis surviving an acute variceal bleeding episode. However, this treatment is associated with a substantial complication rate. Endoscopic band ligation is a newly developed technique in an attempt to provide a safer alternative. The aim of this study was to compare the efficacy and safety of injection sclerotherapy versus variceal ligation in the management of patients with cirrhosis after variceal haemorrhage. METHODS: Seventy-seven patients with cirrhosis who proved to have oesophageal variceal bleeding were studied. After initial control of haemorrhage by sclerotherapy, 40 of the patients were randomly assigned to sclerotherapy and 37 to ligation. Both procedures were performed under midazolam sedation at intervals of 7-14 days until all varices in the distal oesophagus were eradicated or were too small to receive further treatment. RESULTS: The eradication of varices required a lower mean number of sessions with ligation (3.7 +/- 1.9) than with sclerotherapy (5.8 +/- 2.7, p = 0.002). The mean duration of follow-up was similar in both groups (15.6 months +/- 7.3 and 15 +/- 7.4, respectively). The proportion of patients remaining free from recurrent bleeding against time was significantly higher in the ligation group as compared to the sclerotherapy group (chi 2 = 3.86, p = 0.05). Only 13 patients (35%) developed complications in the ligation group as compared to 24 (60%, p = 0.05) in the sclerotherapy group. The mortality rate was similar in both groups (20% and 21%, respectively). CONCLUSIONS: Variceal ligation is better than sclerotherapy in the long-term management of patients with cirrhosis after variceal haemorrhage which was initially controlled with sclerotherapy.     

Pain control after dental surgery: a double-blind, randomised trial of lornoxicam versus morphine

Lornoxicam is a new non-steroidal anti-inflammatory drug of the oxicam class. This randomised, double-blind, placebo controlled trial compared the analgesic efficacy and tolerability of intramuscular (IM) injections of lornoxicam (4, 8, 16 and 20 mg) with morphine (10 and 20 mg) and placebo in 252 patients with mainly moderate to severe pain following surgical removal of an impacted mandibular third molar. Patients treated with lornoxicam or morphine experienced a significantly greater cumulative pain relief over the 4-h post-injection period (TOTPAR0-4) than placebo recipients. This effect appeared to be dose-dependent, with patients in the lornoxicam 4 mg or morphine 10 mg groups recording significantly lower TOTPAR0-4 scores than patients in the higher dosage groups of these drugs. No significant difference was detected between the morphine 20 mg group and the lornoxicam 8, 16 and 20 mg groups. Lornoxicam was well tolerated at all doses and was associated with a significantly lower incidence of adverse events than morphine 10 or 20 mg. Thus, the analgesic efficacy of IM lornoxicam at doses > or = 4 mg is superior to placebo, and doses > or = 8 mg are at least as effective as IM morphine 20 mg. Furthermore, lornoxicam possesses a more favourable tolerability profile than morphine and thus represents an attractive alternative for the treatment of moderate to severe acute pain.     

The analgesic efficacy of tenoxicam versus placebo in day case laparoscopy: a randomised parallel double-blind trial

The analgesic efficacy and duration of action of tenoxicam, an injectable non-steroidal analgesic with a long elimination half-life, were studied in day case laparoscopy in a double-blind randomised prospective parallel placebo-controlled trial. Tenoxicam 20 mg or saline was given intravenously at induction of anaesthesia in 67 women undergoing day case investigative laparoscopy for infertility or abdominal pain. Outcome measures were time to first analgesia, pain levels at 2, 4 and 24 h plus postoperative analgesic consumption in hospital and at home. The study showed no statistically significant difference in any of these measures between the two groups. Tenoxicam 20 mg intravenously immediately pre-operatively cannot be recommended for day case surgery on the basis of this study.