Perioperative growth hormone treatment and functional outcome after major abdominal surgery: a randomized, double-blind, controlled study.
OBJECTIVE: To evaluate short- and long-term effects of perioperative human growth hormone (hGH) treatment on physical performance and fatigue in younger patients undergoing a major abdominal operation in a normal postoperative regimen with oral nutrition. SUMMARY BACKGROUND DATA: Muscle wasting and functional impairment follow major abdominal surgery. METHODS: Twenty-four patients with ulcerative colitis undergoing ileoanal J-pouch surgery were randomized to hGH (12 IU/day) or placebo treatment from 2 days before to 7 days after surgery. Measurements were performed 2 days before and 10, 30, and 90 days after surgery. RESULTS: The total muscle strength of four limb muscle groups was reduced by 7.6% in the hGH group and by 17.1% in the placebo group at postoperative day 10 compared with baseline values. There was also a significant difference between treatment groups in total muscle strength at day 30, and at the 90-day follow-up total muscle strength was equal to baseline values in the hGH group, but still significantly 5.9% below in the placebo group. The work capacity decreased by approximately 20% at day 10 after surgery, with no significant difference between treatment groups. Both groups were equally fatigued at day 10 after surgery, but at day 30 and 90 the hGH patients were less fatigued than the placebo patients. During the treatment period, patients receiving hGH had reduced loss of limb lean tissue mass, and 3 months after surgery the hGH patients had regained more lean tissue mass than placebo patients. CONCLUSIONS: Perioperative hGH treatment of younger patients undergoing major abdominal surgery preserved limb lean tissue mass, increased postoperative muscular strength, and reduced long-term postoperative fatigue. (+info
Single blind, randomised controlled trial of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment in management of genuine stress incontinence in women.
OBJECTIVE: To compare the effect of pelvic floor exercises, electrical stimulation, vaginal cones, and no treatment for genuine stress incontinence. DESIGN: Stratified, single blind, randomised controlled trial. SETTING: Multicentre. PARTICIPANTS: 107 women with clinically and urodynamically proved genuine stress incontinence. Mean (range) age was 49.5 (24-70) years, and mean (range) duration of symptoms 10.8 (1-45) years. INTERVENTIONS: Pelvic floor exercise (n=25) comprised 8-12 contractions 3 times a day and exercise in groups with skilled physical therapists once a week. The electrical stimulation group (n=25) used vaginal intermittent stimulation with the MS 106 Twin at 50 Hz 30 minutes a day. The vaginal cones group (n=27) used cones for 20 minutes a day. The untreated control group (n=30) was offered the use of a continence guard. Muscle strength was measured by vaginal squeeze pressure once a month. MAIN OUTCOME MEASURES: Pad test with standardised bladder volume, and self report of severity. RESULTS: Improvement in muscle strength was significantly greater (P=0.03) after pelvic floor exercises (11.0 cm H2O (95% confidence interval 7.7 to 14.3) before v 19.2 cm H2O (15.3 to 23.1) after) than either electrical stimulation (14.8 cm H2O (10. 9 to 18.7) v 18.6 cm H2O (13.3 to 23.9)) or vaginal cones (11.8 cm H2O (8.5 to 15.1) v 15.4 cm H2O (11.1 to 19.7)). Reduction in leakage on pad test was greater in the exercise group (-30.2 g; -43. 3 to 16.9) than in the electrical stimulation group (-7.4 g; -20.9 to 6.1) and the vaginal cones group (-14.7 g; -27.6 to -1.8). On completion of the trial one participant in the control group, 14 in the pelvic floor exercise group, three in the electrical stimulation group, and two in the vaginal cones group no longer considered themselves as having a problem. CONCLUSION: Training of the pelvic floor muscles is superior to electrical stimulation and vaginal cones in the treatment of genuine stress incontinence. (+info
Symptomatic gastro-oesophageal reflux disease: double blind controlled study of intermittent treatment with omeprazole or ranitidine. The European Study Group.
OBJECTIVE: To assess intermittent treatment over 12 months in patients with symptomatic gastro-oesophageal reflux disease. DESIGN: Randomised, multicentre, double blind, controlled study. Patients with heartburn and normal endoscopy results or mild erosive changes received omeprazole 10 mg or 20 mg daily or ranitidine 150 mg twice daily for 2 weeks. Patients remaining symptomatic had omeprazole 10 mg or ranitidine dose doubled for another 2 weeks while omeprazole 20 mg was continued for 2 weeks. Patients who were symptomatic or mildly symptomatic were followed up for 12 months. Recurrences of moderate or severe heartburn during follow up were treated with the dose which was successful for initial symptom control. SETTING: Hospitals and primary care practices between 1994 and 1996. SUBJECTS: 677 patients with gastro-oesophageal reflux disease. MAIN OUTCOME MEASURES: Total time off active treatment, time to failure of intermittent treatment, and outcomes ranked from best to worst. RESULTS: 704 patients were randomised, 677 were eligible for analyses; 318 reached the end of the study with intermittent treatment without recourse to maintenance antisecretory drugs. The median number of days off active treatment during follow up was 142 for the entire study (281 for the 526 patients who reached a treatment related end point). Thus, about half the patients did not require treatment for at least 6 months, and this was similar in all three treatment groups. According to outcome, 378 (72%) patients were in the best outcome ranks (no relapse or one (or more) relapse but in remission until 12 months); 630 (93%) had three or fewer relapses in the intermittent treatment phase. Omeprazole 20 mg provided faster relief of heartburn. The results were similar in patients with erosive and non-erosive disease. CONCLUSIONS: Intermittent treatment is effective in managing symptoms of heartburn in half of patients with uncomplicated gastro-oesophageal reflux disease. It is simple and applicable in general practice, where most patients are seen. (+info
Optimal thrombolytic strategies for acute myocardial infarction--bolus administration.
Optimal strategies for thrombolysis in myocardial infarction (TIMI) are still being sought because the TIMI 3 flow rates achievable using standard regimens average approximately 60%. Double bolus administration of recombinant tissue plasminogen activator (tPA) is a novel approach with potential for earlier patency combined with ease of administration. We reviewed total patency rates, TIMI 3 patency rates, mortality, stroke and intracranial haemorrhage rates in the major trials of accelerated infusion tPA/bolus tPA/reteplase in acute myocardial infarction. A direct comparison was performed with results of two recent trials of double bolus (two 50 mg boli, 30 min apart) vs. accelerated infusion tPA: the Double Bolus Lytic Efficacy Trial (DBLE), an angiographic study, and the COBALT Trial, a mortality study. The DBLE trial showed equivalent patency rates for accelerated infusion and double bolus administration of tPA. Reviewing other angiographic trials, total patency and TIMI 3 patency rates achievable with double bolus tPA were comparable to those with accelerated infusion tPA or bolus reteplase administration. The COBALT study demonstrated a 30-day mortality of 7.53% in patients treated with accelerated infusion tPA compared with 7.98% for double bolus tPA treated patients. The small excess in mortality with double bolus treatment was confined to the elderly; in those < or = 75 years, mortality rates were 5.6% and 5.7%, for double bolus and accelerated infusion, respectively, and rates for death or non-fatal stroke were 6.35% and 6.3%, respectively. Comparison with other trials demonstrated mortality, stroke and intracranial haemorrhage rates with double bolus treatment similar to those associated with either accelerated infusion tPA or bolus reteplase treatment. Double bolus administration of tPA to patients with acute myocardial infarction is associated with total patency, TIMI 3 patency, mortality, stroke and intracranial haemorrhage rates similar to those associated with either accelerated infusion of tPA or bolus reteplase. (+info
Late referral of end-stage renal failure.
We studied all new patients accepted for renal replacement therapy (RRT) in one unit from 1/1/96 to 31/12/97 (n = 198), to establish time from nephrology referral to RRT, evidence of renal disease prior to referral and the adequacy of renal management prior to referral. Sixty four (32.3%, late referral group) required RRT within 12 weeks of referral. Fifty-nine (29.8%) had recognizable signs of chronic renal failure > 26 weeks prior to referral. Patients starting RRT soon after referral were hospitalized for significantly longer on starting RRT (RRT within 12 weeks of referral, median hospitalization 25.0 days (n = 64); RRT > 12 weeks after referral, median 9.7 days (n = 126), (p < 0.001)). Observed survival at 1 year was 68.3% overall, with 1-year survival of the late referral and early referral groups being 60.5% and 72.5%, respectively (p = NS). Hypertension was found in 159 patients (80.3%): 46 (28.9%) were started on antihypertensive medication following referral, while a further 28 (17.6%) were started on additional antihypertensives. Of the diabetic population (n = 78), only 26 (33.3%) were on an angiotensin-converting-enzyme inhibitor (ACEI) at referral. Many patients are referred late for dialysis despite early signs of renal failure, and the pre-referral management of many of the patients, as evidenced by the treatment of hypertension and use of ACEI in diabetics, is less than optimal. (+info
Tumour ablation and hepatic decompensation rates in multi-agent chemoembolization of hepatocellular carcinoma.
Thirty-seven cirrhotic patients with 62 hepatocellular carcinoma (HCC) foci--most Child-Pugh class B or C and/or with large, inoperable tumours--underwent 148 sessions of transcatheter arterial chemoembolization (TACE) using lipiodol, doxorubicin and cisplatin. Treatment efficacy was assessed by serial hepatic arteriography in 34/37 (91.9%) patients and abdominal CT scanning in 3/37 (8.1%) patients. Child-Pugh status was determined prior to each treatment session. Varying degrees of control of tumour neovascularity occurred for a median 390 days (range 90 to > 1680 days) in 33/34 (97.1%) patients in whom progress hepatic arteriography was performed. Ablation of tumour neovascularity occurred in 6/6 (100%), 4/12 (33.3%) and 6/16 (37.5%) patients with HCC diameters < 4 cm, 4-7 cm and > 8 cm, respectively (p < 0.02). Significantly more sessions were required for ablation of larger tumours (p < 0.05). Recurrent HCC was detected in 50% of patients after a median 240 days (range 60-1120 days). Deterioration in Child-Pugh status followed a session of TACE on 19/148 (12.8%) occasions but resulted in unscheduled hospitalization on only 4/148 (2.7%) occasions, the highest incidence (8.3%) in Child-Pugh C patients. Actuarial survival was 27/36 (75.0%) at 6 months, 17/34 (50.0%) at 12 months, 14/34 (41.2%) at 18 months, 9/31 (29.0%) at 24 months and 4/27 (14.8%) at 36 months. Multi-agent TACE with lipiodol, doxorubicin and cisplatin provides a useful anti-tumour effect, even in cirrhotic patients with large HCCs. The incidence of clinically significant deterioration in hepatic function due to ischaemia of non-tumorous liver is acceptably low, even in Child-Pugh C patients. (+info
Interferon-alpha does not improve outcome at one year in patients with diffuse cutaneous scleroderma: results of a randomized, double-blind, placebo-controlled trial.
OBJECTIVE: To determine whether interferon-alpha (IFNalpha) reduces the severity of skin involvement in early (<3 years) diffuse scleroderma. METHODS: In a randomized, placebo-controlled, double-blind trial, 35 patients with early scleroderma received subcutaneous injections of either IFNalpha (13.5 x 10(6) units per week in divided doses) or indistinguishable placebo. Outcomes assessed were the modified Rodnan skin score, as determined by a single observer at baseline, 6 months, and 12 months, as well as data on renal, cardiac, and lung function. Pre- and posttreatment skin biopsy samples were analyzed and blood was obtained for assessment of procollagen peptide levels. RESULTS: There were 11 withdrawals from the IFNalpha group and 3 from the placebo group due to either toxicity, lack of efficacy, or death. In the intent-to-treat analysis, there was a greater improvement in the skin score in the placebo group between 0 and 12 months (mean change IFNalpha -4.7 versus placebo -7.5; P = 0.36). There was also a greater deterioration in lung function in patients receiving active therapy, as assessed by either the forced vital capacity (mean change IFNalpha -8.2 versus placebo +1.3; P = 0.01) or the diffusing capacity for carbon monoxide (mean change IFNalpha -9.3 versus placebo +4.7; P = 0.002). Skin biopsy showed no significant decrease in collagen synthesis in the IFNalpha group, and no significant differences in the levels of procollagen peptides were seen between the 2 groups. CONCLUSION: This study suggests that IFNalpha is of no value in the treatment of scleroderma, and that it may in fact be deleterious. (+info
Economic consequences of the progression of rheumatoid arthritis in Sweden.
OBJECTIVE: To develop a simulation model for analysis of the cost-effectiveness of treatments that affect the progression of rheumatoid arthritis (RA). METHODS: The Markov model was developed on the basis of a Swedish cohort of 116 patients with early RA who were followed up for 5 years. The majority of patients had American College of Rheumatology (ACR) functional class II disease, and Markov states indicating disease severity were defined based on Health Assessment Questionnaire (HAQ) scores. Costs were calculated from data on resource utilization and patients' work capacity. Utilities (preference weights for health states) were assessed using the EQ-5D (EuroQol) questionnaire. Hypothetical treatment interventions were simulated to illustrate the model. RESULTS: The cohort distribution among the 6 Markov states clearly showed the progression of the disease over 5 years of followup. Costs increased with increasing severity of the Markov states, and total costs over 5 years were higher for patients who were in more severe Markov states at diagnosis. Utilities correlated well with the Markov states, and the EQ-5D was able to discriminate between patients with different HAQ scores within ACR functional class II. CONCLUSION: The Markov model was able to assess disease progression and costs in RA. The model can therefore be a useful tool in calculating the cost-effectiveness of different interventions aimed at changing the progression of the disease. (+info