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PubMed2000

Early use of non-invasive ventilation for acute exacerbations of chronic obstructive pulmonary disease on general respiratory wards: a multicentre randomised controlled trial.

BACKGROUND: Within the intensive-care unit, non-invasive ventilation (NIV) can prevent the need for intubation and the mortality associated with severe episodes of chronic obstructive pulmonary disease (COPD). The aim of this study was to find whether the introduction of NIV, early after the admission on a general respiratory ward, was effective at reducing the need for intubation and the mortality associated with acute exacerbations of COPD. METHODS: We did a prospective multicentre randomised controlled study comparing NIV with standard therapy in patients with mild to moderate acidosis. NIV was administered on the ward with a simple non-invasive ventilator and a standardised predefined protocol. Patients were recruited from 14 UK hospitals over 22 months. FINDINGS: 236 patients were recruited, 118 received standard therapy alone and 118 additional NIV. The two groups had similar characteristics at enrolment. The use of NIV significantly reduced the need for intubation as defined by the failure criteria. 32/118 (27%) of the standard group failed compared with 18/118 (15%) of the NIV group (p=0.02). In-hospital mortality was also reduced by NIV, 24/118 (20%) died in the standard group compared with 12/118 (10%) in the NIV group (p=0.05). In both groups pH, PaCO2, and respiratory rate improved at 4 h (p<0.01). However, NIV led to a more rapid improvement in pH in the first hour (p=0.02) and a greater fall in respiratory rate at 4 h (p=0.035). The duration of breathlessness was also reduced by NIV (p=0.025). INTERPRETATION: The early use of NIV for mildly and moderately acidotic patients with COPD in the general ward setting leads to more rapid improvement of physiological variables, a reduction in the need for invasive mechanical ventilation (with objective criteria), and a reduction in in-hospital mortality.

Aged↗
PubMed2000

Early prediction of severity in acute pancreatitis by urinary trypsinogen activation peptide: a multicentre study.

BACKGROUND: There is a pressing clinical requirement for an early simple test of severity in acute pancreatitis. We investigated the use of an assay of trypsinogen activation peptide (TAP). METHODS: We undertook a multicentre study in 246 patients (172 with acute pancreatitis [35 with severe disease], 74 controls). We assessed the predictive value of urinary TAP concentrations measured by a validated competitive immunoassay. We compared the results with those for plasma C-reactive protein and three clinicobiochemical scoring systems. TAP and C-reactive protein concentrations were analysed at set times after symptom onset and compared with the clinicobiochemical systems scores at key times during hospital stay. FINDINGS: At 24 h after symptom onset, the median urinary TAP concentration was 37 nmol/L (IQR 17-110) for severe and 15 nmol/L (5-35) for mild disease (p<0.001). The respective values for plasma C-reactive protein were 24 mg/L (3-34) and 25 mg/L (6-75; p=0.208). The sensitivity, specificity, positive predictive, and negative predictive values of the test to show severe acute pancreatitis compared with mild acute pancreatitis at 24 h were: for TAP (>35 nmol/L), 58%, 73%, 39%, and 86%, respectively, and for C-reactive protein (>150 mg/L), 0%, 90%, 0%, and 75%. 48 h after admission the values for the clinicobiochemical scoring systems were: APACHE II (> or =8), 56%, 64%, 30%, and 85%; Ranson score (> or =3), 89%, 64%, 38%, and 96%; and Glasgow score (> or =3), 77%, 75%, 44%, and 93%. At 48 h, the values for C-reactive protein were 86%, 61%, 37%, and 94% and for TAP were 83%, 72%, 44%, and 94%. Combined testing of C-reactive protein and TAP was not superior to TAP alone for accuracy. INTERPRETATION: Urinary TAP provided accurate severity prediction 24 h after onset of symptoms. This single marker of severity in acute pancreatitis deserves routine clinical application.

Acute Disease↗
PubMed2000

Efficacy of sirolimus compared with azathioprine for reduction of acute renal allograft rejection: a randomised multicentre study. The Rapamune US Study Group.

BACKGROUND: Acute rejection episodes after renal transplantation are an important clinical challenge, despite use of multidrug immunosuppressive regimens. We did a prospective, multicentre, randomised, double-blind trial to investigate the impact of the addition of sirolimus, compared with azathioprine, to a cyclosporin and prednisone regimen. METHODS: 719 recipients of primary HLA-mismatched cadaveric or living-donor renal allografts who displayed initial graft function were randomly assigned, after transplantation, sirolimus 2 mg daily (n=284) or 5 mg daily (n=274), or azathioprine (n=161). We assessed the primary composite endpoint of efficacy failure, occurrence of biopsy-confirmed acute rejection episodes, graft loss, or death, and various secondary endpoints that characterise these episodes at 6 months and 12 months. Analyses were done by intention to treat. FINDINGS: The rate of efficacy failure at 6 months was lower in the two sirolimus groups (2 mg 18.7%, p=0.002; 5 mg 16.8%, p<0.001) than in the azathioprine group (32.3%). The frequency of biopsy-confirmed acute rejection episodes was also lower (2 mg 16.9%, p=0.002; 5 mg 12.0%, p<0.001; azathioprine 29.8%). At 12 months, survival was similar in all groups for grafts (97.2%, 96.0%, and 98.1%) and patients (94.7%, 92.7%, and 93.8%). Patients on sirolimus showed a delay in the time to first acute rejection episode and decreased frequency of moderate and severe histological grades of rejection episodes and related antibody treatment, compared with the azathioprine group. Rates of infection and malignant disorders were similar in all groups. INTERPRETATION: Use of sirolimus reduced occurrence and severity of biopsy-confirmed acute rejection episodes with no increase in complications. Further studies are needed to establish the optimum doses for the combined regimen.

Acute Disease↗
PubMed2000

Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: a multicentre study.

BACKGROUND: Ventricular arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot are devastating complications in adult survivors of early surgery, but their prediction remains difficult. METHODS: We examined surgical, electrocardiographic, and late haemodynamic data, and their relation to clinical arrhythmia and sudden death occurring over 10 years, in a multicentre cohort of patients with repaired tetralogy, who were alive in 1985. RESULTS: Of 793 patients (mean age at repair 8.2 years [SD 8], mean time from repair 21.1 years [8.7]) who entered the study, 33 patients developed sustained monomorphic ventricular tachycardia, 16 died suddenly, and 29 had new-onset sustained atrial flutter or fibrillation. Electrocardiographic markers (QRS duration, QRS rate of change between 1985 and 1995) were significantly greater in the ventricular tachycardia and sudden-death groups. Older age at repair was associated with a higher risk of sudden death and atrial tachyarrhythmia. Pulmonary regurgitation was the main underlying haemodynamic lesion for patients with ventricular tachycardia and sudden death, whereas tricuspid regurgitation was for those with atrial flutter/fibrillation. Despite adverse haemodynamics, no patient who died suddenly had undergone late reoperation. CONCLUSION: Arrhythmia and sudden death are important late sequelae for patients after repair of tetralogy of Fallot. The electrophysiological and haemodynamic substrate of sudden death resembled that of sustained ventricular tachycardia, with pulmonary regurgitation being the predominant haemodynamic lesion. Preservation or restoration of pulmonary valve function may thus reduce the risk of sudden death. Furthermore, electrocardiographic markers can help to identify patients at risk.

Adult↗
PubMed2001

Cognitive behaviour therapy for chronic fatigue syndrome: a multicentre randomised controlled trial.

BACKGROUND: Cognitive behaviour therapy (CBT) seems a promising treatment for chronic fatigue syndrome (CFS), but the applicability of this treatment outside specialised settings has been questioned. We compared CBT with guided support groups and the natural course in a randomised trial at three centres. METHODS: Of 476 patients diagnosed with CFS, 278 were eligible and willing to take part. 93 were randomly assigned CBT (administered by 13 therapists recently trained in this technique for CFS), 94 were assigned the support-group approach, and 91 the control natural course. Multidimensional assessments were done at baseline, 8 months, and 14 months. The primary outcome variables were fatigue severity (on the checklist individual strength) and functional impairment (on the sickness impact profile) at 8 and 14 months. Data were analysed by intention to treat. FINDINGS: 241 patients had complete data (83 CBT, 80 support groups, 78 natural course) at 8 months. At 14 months CBT was significantly more effective than both control conditions for fatigue severity (CBT vs support groups 5.8 [2.2-9.4]; CBT vs natural course 5.6 [2.1-9.0]) and for functional impairment (CBT vs support groups 263 [38-488]; CBT vs natural course 222 [3-441]). Support groups were not more effective for CFS patients than the natural course. Among the CBT group, clinically significant improvement was seen in fatigue severity for 20 of 58 (35%), in Karnofsky performance status for 28 of 57 (49%), and self-rated improvement for 29 of 58 (50%). Prognostic factors for outcome after CBT were a higher sense of control predicting more improvement, and a passive activity pattern and focusing on bodily symptoms predicting less improvement. INTERPRETATION: CBT was more effective than guided support groups and the natural course in a multicentre trial with many therapists. Our study showed a lower proportion of patients with improvement than CBT trials with a few highly skilled therapists.

Adult↗
PubMed2001

Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study.

BACKGROUND: Hydroxyethylstarch used for volume restoration in brain-dead kidney donors has been associated with impaired kidney function in the transplant recipients. We undertook a multicentre randomised study to assess the frequency of acute renal failure (ARF) in patients with severe sepsis or septic shock treated with hydroxyethylstarch or gelatin. METHODS: Adults with severe sepsis or septic shock were enrolled prospectively in three intensive-care units in France. They were randomly assigned 6% hydroxyethylstarch (200 kDa, 0.60-0.66 substitution) or 3% fluid-modified gelatin. The primary endpoint was ARF (a two-fold increase in serum creatinine from baseline or need for renal replacement therapy). Analyses were by intention to treat. FINDINGS: 129 patients were enrolled over 18 months. Severity of illness and serum creatinine (median 143 [IQR 88-203] vs 114 [91-175] micromol/L) were similar at baseline in the hydroxyethylstarch and gelatin groups. The frequencies of ARF (27/65 [42%] vs 15/64 [23%], p=0.028) and oliguria (35/62 [56%] vs 23/63 [37%], p=0.025) and the peak serum creatinine concentration (225 [130-339] vs 169 [106-273] micromol/L, p=0.04) were significantly higher in the hydroxyethylstarch group than in the gelatin group. In a multivariate analysis, risk factors for acute renal failure included mechanical ventilation (odds ratio 4.02 [95% CI 1.37-11.8], p=0.013) and use of hydroxyethylstarch (2.57 [1.13-5.83], p=0.026). INTERPRETATIONS: The use of this preparation of hydroxyethylstarch as a plasma-volume expander is an independent risk factor for ARF in patients with severe sepsis or septic shock.

Acute Kidney Injury↗
PubMed2001

Platinum-based and non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a randomised multicentre trial.

BACKGROUND: Docetaxel in combination with cisplatin or gemcitabine are active chemotherapy reigimes against non-small-cell lung cancer. We compared the efficacy and safety of a combination of cisplatin and docetaxel (group 1) with that of gemcitabine and docetaxel (group 2) in the treatment of advanced non-small-cell lung cancer in a prospective, randomised, multicentre trial. METHODS: Patients with stage IIIB or IV lung cancer who had not had prior chemotherapy were allocated either to group 1 and treated with docetaxel (100 mg/m(2), day 1) and cisplatin (80 mg/m(2), day 2) or to group 2 and treated with gemcitabine (1100 mg/m(2), days 1 and 8) and docetaxel (100 mg/m(2), day 8). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)). All patients received recombinant human granulocyte colony-stimulating factor (150 mg/m(2)) had appropriate standard premedication. Response and toxicity were assessed using WHO criteria. Analysis was by intention to treat. FINDINGS: 441 patients were randomly assigned to receive docetaxel/cisplatin (group 1, n=219) or gemcitabine/docetaxel (group 2, n=222). 14 patients in group 1 and 21 patients in group 2 were not evaluable. Objective response rates were similar in the two groups: group 1, 32.4% (95% CI 26.2-38.6%; 1.4% complete response and 31% partial response); group 2, 30.2% (24.5-36.2%; 0.9% complete response and 29.3% partial response). The two groups did not differ in median duration of response, time to tumour progression, overall survival, or 1 year or 2 year survival rates. INTERPRETATION: Both drug combinations had comparable activity in patients with advanced cancer who had not previously had chemotherapy; however, gemcitabine and docetaxel had the most favourable toxicity profile.

Aged↗
PubMed2001

WHO multicentre randomised trial of misoprostol in the management of the third stage of labour.

BACKGROUND: Postpartum haemorrhage is a leading cause of maternal morbidity and mortality. Active management of the third stage of labour, including use of a uterotonic agent, has been shown to reduce blood loss. Misoprostol (a prostaglandin E1 analogue) has been suggested for this purpose because it has strong uterotonic effects, can be given orally, is inexpensive, and does not need refrigeration for storage. We did a multicentre, double-blind, randomised controlled trial to determine whether oral misoprostol is as effective as oxytocin during the third stage of labour. METHODS: In hospitals in Argentina, China, Egypt, Ireland, Nigeria, South Africa, Switzerland, Thailand, and Vietnam, we randomly assigned women about to deliver vaginally to receive 600 microg misoprostol orally or 10 IU oxytocin intravenously or intramuscularly, according to routine practice, plus corresponding identical placebos. The medications were administered immediately after delivery as part of the active management of the third stage of labour. The primary outcomes were measured postpartum blood loss of 1000 mL or more, and the use of additional uterotonics without an unacceptable level of side-effects. We chose an upper limit of a 35% increase in the risk of blood loss of 1000 mL or more as the margin of clinical equivalence, which was assessed by the confidence interval of the relative risk. Analysis was by intention to treat. FINDINGS: 9264 women were assigned misoprostol and 9266 oxytocin. 37 women in the misoprostol group and 34 in the oxytocin group had emergency caesarean sections and were excluded. 366 (4%) of women on misoprostol had a measured blood loss of 1000 mL or more, compared with 263 (3%) of those on oxytocin (relative risk 1.39 [95% CI 1.19-1.63], p<0.0001). 1398 (15%) women in the misoprostol group and 1002 (11%) in the oxytocin group required additional uterotonics (1.40 [1.29-1.51], p<0.0001). Misoprostol use was also associated with a significantly higher incidence of shivering (3.48 [3.15-3.84]) and raised body temperature (7.17 [5.67-9.07]) in the first hour after delivery. INTERPRETATION: 10 IU oxytocin (intravenous or intramuscular) is preferable to 600 microg oral misoprostol in the active management of the third stage of labour in hospital settings where active management is the norm.

Adult↗
PubMed2001

Postoperative enteral versus parenteral nutrition in malnourished patients with gastrointestinal cancer: a randomised multicentre trial.

BACKGROUND: Although current opinion favours the use of enteral over parenteral nutrition, the clinical benefits of early postoperative nutrition in patients undergoing elective surgery have never been clearly shown. We aimed to test the hypothesis that postoperative enteral nutrition is better (fewer postoperative complications) than parenteral nutrition containing similar energy and nitrogen amounts (112 kJ kg(-1) day(-1) and 1.4 g aminoacid kg(-1) day(-1)). METHODS: We did a randomised multicentre clinical trial in patients with gastrointestinal cancer who were malnourished and candidates for major elective surgery. 159 patients were assigned to enteral nutrition and 158 to parenteral nutrition. The primary endpoint was the occurrence of postoperative complications, and secondary endpoints were length of postoperative hospital stay, adverse effects, and treatment crossover. Analysis was by intention to treat. FINDINGS: Postoperative complications occurred in 54 (34%) patients fed enterally versus 78 (49%) fed parenterally (relative risk 0.69, 95% CI 0.53-0.90, p=0.005). Length of postoperative stay was 13.4 days and 15.0 days in the enteral nutrition and parenteral nutrition groups, respectively (p=0.009). Adverse effects occurred in 56 (35%) patients fed enterally versus 22 (14%) patients fed parenterally (2.50, 1.61-3.86, p<0.0001). 14 (9%) patients on enteral nutrition had to switch to parenteral nutrition, whereas none of those fed parenterally crossed over to enteral feeding. INTERPRETATION: We conclude that early enteral nutrition significantly reduces the complication rate and duration of postoperative stay compared with parenteral nutrition, although parenteral nutrition is better tolerated than enteral nutrition.

Comorbidity↗
PubMed2002

Intravenous immunoglobulin or high-dose methylprednisolone, with or without oral prednisone, for adults with untreated severe autoimmune thrombocytopenic purpura: a randomised, multicentre trial.

BACKGROUND: Treatment of adults with autoimmune thrombocytopenic purpura (AITP) is based more on individual experience than on results of controlled studies. We compared intravenous immunoglobulin with high-dose methylprednisolone in untreated adults with severe AITP and assessed efficacy of subsequent oral steroids compared with placebo. Primary outcome was number of days with platelet count greater than 50 x 10(9)/L within the first 21 days. METHODS: We did a randomised multicentre trial based on a 232 design. 122 adults with severe AITP (platelet count < or =20 x 10(9)/L) were randomly assigned to receive either intravenous immunoglobulin or high-dose methylprednisolone on days 1-3 (randomisation A), and then to receive either oral prednisone or placebo (randomisation B) on days 4-21. Analysis was by intention to treat. FINDINGS: Six patients were excluded from the analysis. The number of days on which platelet counts were above 50 x 10(9)/L was 18 in 56 patients receiving intravenous immunoglobulin and 14 in 60 receiving high-dose methylprednisolone (p=0.02). Percentage of patients who had platelet counts over 50 x 10(9)/L on days 2 and 5 was 7% and 79%, respectively, in the intravenous immunoglobulin group compared with 2% and 60%, respectively, in the high-dose methylprednisolone group (p=0.04). During the second treatment period, prednisone was more effective than placebo for all short-term endpoints. Patients who received intravenous immunoglobulin and prednisone had platelet count greater than 50 x 10(9)/L for 18.5 days (p=0.005), and those treated with high-dose methylprednisolone and prednisone had this count for 17.5 days. INTERPRETATION: Intravenous immunoglobulin and oral prednisone seems to be more effective than high-dose methylprednisolone and oral prednisone in adults with severe AITP, although the latter treatment is effective and well tolerated.

Adult↗
PubMed2002

Efficacy and safety of tacrolimus compared with ciclosporin microemulsion in renal transplantation: a randomised multicentre study.

BACKGROUND: In previous comparative studies tacrolimus was superior to the standard formulation of ciclosporin in preventing acute rejection after renal transplantation. We have compared the microemulsion formulation of ciclosporin with tacrolimus in a multicentre randomised trial. METHODS: The 6-month open study involved 560 patients in 50 European centres. 287 patients were randomly assigned tacrolimus and 273 ciclosporin microemulsion plus azathioprine and corticosteroids. The initial oral daily doses were 0.30 mg/kg for tacrolimus and 8-10 mg/kg for ciclosporin. The primary endpoint was the proportion of patients with biopsy-proven acute rejection and the time to this event. FINDINGS: The two study groups were similar in terms of baseline characteristics. Three patients did not receive study treatment or did not undergo transplantation (one tacrolimus, two ciclosporin). The rate of biopsy-confirmed acute rejection was significantly lower with tacrolimus than with ciclosporin microemulsion (56 patients [19.6%] vs 101 [37.3%]; 17.7% difference [95% CI 10.3-25.1]; p<0.0001). Biopsy-confirmed corticosteroid-resistant rejection was also significantly lower with tacrolimus (27 [9.4%] vs 57 [21.0%]; 11.6% difference [5.7-17.5]; p<0.0001). Cross-over between therapies because of biopsy-proven rejection was judged necessary in one of 286 (0.3%) tacrolimus-group patients and 27 of 271 (10.0%) ciclosporin-group patients (p<0.0001). There were no significant differences in survival of patients or grafts or in renal function. The overall frequency of adverse events was similar in the two groups, though hypertension and hypercholesterolaemia were more common in the ciclosporin group and tremor and hypomagnesaemia were more frequent in the tacrolimus group. INTERPRETATION: Tacrolimus was significantly more effective than ciclosporin microemulsion in preventing acute rejection after renal transplantation and had a superior cardiovascular-risk profile.

Adolescent↗
PubMed2002

Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial.

UNLABELLED: BACKGROUND Treatment options for patients with ankylosing spondylitis are few. We aimed to assess the effectiveness of infliximab, an antibody to tumour necrosis factor (TNF)-alpha, in treatment of such patients. METHODS: In this 12-week placebo-controlled multicentre study, we randomly assigned 35 patients with active ankylosing spondylitis to intravenous infliximab (5 mg/kg) and 35 to placebo at weeks 0, 2, and 6. One patient in the infliximab group was withdrawn from the study. Our primary outcome was regression of disease activity of at least 50%. To assess response, we used validated clinical criteria from the ankylosing spondylitis assessment working group, including disease activity (BASDAI), functional indices (BASFI), metrology (BASMI), and quality of life (short form 36). Analyses were done by intention to treat. FINDINGS: 18 (53%) of 34 patients on infliximab had a regression of disease activity at week 12 of at least 50% compared with three (9%) of 35 on placebo (difference 44% [95% CI 23-61], p<0.0001). Function and quality of life also improved significantly on infliximab but not on placebo (p<0.0001 and p<0.0001, respectively). Treatment with infliximab was generally well tolerated, but three patients had to stop treatment because of systemic tuberculosis, allergic granulomatosis of the lung, or mild leucopenia. INTERPRETATION: Our results show that treatment with infliximab is effective in patients with active ankylosing spondylitis. Since there are some potentially serious adverse effects, we recommend that this treatment mainly be used in co-operation with rheumatological centres.

Adult↗
PubMed2002

Every-other-day interferon beta-1b versus once-weekly interferon beta-1a for multiple sclerosis: results of a 2-year prospective randomised multicentre study (INCOMIN).

BACKGROUND: The three interferon beta preparations approved for treatment of relapsing-remitting multiple sclerosis (MS) differ in dose and frequency of administration. Interferon beta-1a 30 microg is administered once a week, interferon beta-1a 22 microg or 44 microg is given three times a week, and interferon beta-1b 250 microg is administered on alternate days. No clinical study directly comparing the different regimens has been published. The INCOMIN study was designed to compare the clinical and magnetic resonance imaging (MRI) benefits of on-alternate-day interferon beta-1b 250 microg with once-weekly interferon beta-1a 30 microg. METHODS: INCOMIN was a 2-year, prospective, randomised, multicentre study. 188 patients with relapsing-remitting MS were assigned to interferon beta-1b (n=96) or interferon beta-1a (n=92). Primary outcome measures were the proportion of patients free from relapses and that of patients free from new proton density/T2 lesions at MRI assessment. Several secondary outcome measures were also assessed. Analysis was by intention to treat. FINDINGS: Over 2 years, 49 (51%) individuals administered interferon beta-1b remained relapse-free compared with 33 (36%) given interferon beta-1a relative risk of relapse 0.76; 95% CI 0.59-0.9; p=0.03); and 42 (55%) compared with 19 (26%), respectively, remained free from new T2 lesions at MRI (relative risk of new T2 lesion 0.6; 0.45-0.8; p<0.0003). In both groups, the differences between the two treatments increased during the second year. There were also significant differences in favour of interferon beta-1b in most of the secondary outcome measures, including delay of confirmed disease progression. INTERPRETATION: High-dose interferon beta-1b administered every other day is more effective than interferon beta-1a given once a week.

Adjuvants, Immunologic↗
PubMed2002

Diagnostic strategy for patients with suspected pulmonary embolism: a prospective multicentre outcome study.

BACKGROUND: We designed a prospective multicentre outcome study to evaluate a diagnostic strategy based on clinical probability, spiral CT, and venous compression ultrasonography of the legs in patients with suspected pulmonary embolism (PE). The main aim was to assess the safety of withholding anticoagulant treatment in patients with low or intermediate clinical probability of PE and negative findings on spiral CT and ultrasonography. METHODS: 1041 consecutive inpatients and outpatients with suspected PE were included. Patients with negative spiral CT and ultrasonography and clinically assessed as having a low or intermediate clinical probability were left untreated. Those with high clinical probability underwent lung scanning, pulmonary angiography, or both. All patients were followed up for 3 months. FINDINGS: PE was diagnosed in 360 (34.6%) patients; 55 had positive ultrasonography despite negative spiral CT. Of 601 patients with negative spiral CT and ultrasonography, 76 were clinically assessed as having a high probability of PE; lung scanning or angiography showed PE in four (5.3% [95% CI 1.5-13.1]). The remaining 525 patients were assessed as having low or intermediate clinical probability, and 507 of them were not treated. Of these patients, nine experienced venous thromboembolism during follow-up (1.8% [0.8-3.3]). The diagnostic strategy proved inconclusive in 95 (9.1%) patients, and pulmonary angiography was done in 74 (7.1%). INTERPRETATION: Withholding of anticoagulant therapy is safe when the clinical probability of PE is assessed as low or intermediate and spiral CT and ultrasonography are negative.

Adult↗
PubMed2003

Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Renal transplant recipients are at increased risk of premature cardiovascular disease. Although statins reduce cardiovascular risk in the general population, their efficacy and safety in renal transplant recipients have not been established. We investigated the effects of fluvastatin on cardiac and renal endpoints in this population. METHODS: We did a multicentre, randomised, double-blind, placebo-controlled trial in 2102 renal transplant recipients with total cholesterol 4.0-9.0 mmol/L. We randomly assigned patients fluvastatin (n=1050) or placebo (n=1052) and follow up was for 5-6 years. The primary endpoint was the occurrence of a major adverse cardiac event, defined as cardiac death, non-fatal myocardial infarction (MI), or coronary intervention procedure. Secondary endpoints were individual cardiac events, combined cardiac death or non-fatal MI, cerebrovascular events, non-cardiovascular death, all-cause mortality, and graft loss or doubling of serum creatinine. Analysis was by intention to treat. FINDINGS: After a mean follow-up of 5.1 years, fluvastatin lowered LDL cholesterol concentrations by 32%. Risk reduction with fluvastatin for the primary endpoint (risk ratio 0.83 [95% CI 0.64-1.06], p=0.139) was not significant, although there were fewer cardiac deaths or non-fatal MI (70 vs 104, 0.65 [0.48-0.88] p=0.005) in the fluvastatin group than in the placebo group. Coronary intervention procedures and other secondary endpoints did not differ significantly between groups. INTERPRETATION: Although cardiac deaths and non-fatal MI seemed to be reduced, fluvastatin did not generally reduce rates of coronary intervention procedures or mortality. Overall effects of fluvastatin were similar to those of statins in other populations.

Adult↗
PubMed2003

Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study.

BACKGROUND: Multiple organ dysfunction syndrome is more frequent than death in paediatric intensive care units. Estimation of the severity of this syndrome could be a useful additional outcome measure in clinical trials in such units. We aimed to validate the paediatric logistic organ dysfunction (PELOD) score and estimate its validity when recorded daily (dPELOD). METHODS: We did a prospective, observational, multicentre cohort study in seven multidisciplinary, tertiary-care paediatric intensive care units of university-affiliated hospitals (two French, three Canadian, and two Swiss). We included 1806 consecutive patients (median age 24 months; IQR 5-90). PELOD score includes six organ dysfunctions and 12 variables and was recorded daily. For each variable, the most abnormal value each day and during the whole stay were used in calculating the dPELOD and PELOD scores, respectively. Outcome was vital status at discharge. We used Hosmer-Lemeshow goodness-of-fit tests to evaluate calibration and areas under receiver operating characteristic curve (AUC) to estimate discrimination. FINDINGS: 370 (21%) patients had no organ dysfunction, 471 (26%) had one, 457 (25%) had two, and 508 (28%) had three or more. Case fatality rate was 6.4% (115 deaths). PELOD score was significantly higher in non-survivors (mean 31.0 [SE 1.2]) than survivors (9.4 [0.2]; p<0.0001). Calibration (p=0.54) and discrimination (AUC=0.91, SE=0.01) of PELOD and dPELOD (p> or =0.39; AUC> or =0.79) scores were good. INTERPRETATION: PELOD and dPELOD scores are valid outcome measures of the severity of multiple organ dysfunction syndrome in paediatric intensive care units; their use should significantly reduce the sample size required to complete clinical trials in critically ill children.

Adolescent↗
PubMed2003

Local, regional, or general anaesthesia in groin hernia repair: multicentre randomised trial.

BACKGROUND: In specialised centres, local anaesthesia is almost always used in groin hernia surgery; whereas in routine surgical practice, regional or general anaesthesia are the methods of choice. In this three-arm multicentre randomised trial, we aimed to compare the three methods of anaesthesia and to determine the extent to which general surgeons can reproduce the excellent results obtained with local anaesthesia in specialised hernia centres. METHODS: Between January, 1999, and December, 2001, 616 patients at ten hospitals, were randomly assigned to have either local, regional, or general anaesthesia. Primary endpoints were early and late postoperative complications. Secondary endpoints were duration of surgery and anaesthesia, length of postoperative hospital stay, and time to normal activity. Analysis was by intention to treat. FINDINGS: Intraoperative tolerance for local anaesthesia was high. In the early postoperative period, local anaesthesia was superior to the other two types with respect to almost all endpoints. At 8 days' and 30 days' follow-up, there were no significant differences between the three groups. Although the mean duration of surgery was longer, the total anaesthesia time-ie, time from the start of anaesthesia until the patient left the operating room-was significantly shorter than it was for regional or general anaesthesia. INTERPRETATION: Local anaesthesia has substantial advantages compared with regional or general anaesthesia, such as shorter duration of admission, less postoperative pain, and fewer micturition difficulties. The favourable results obtained with local anaesthesia in specialised hernia centres can, to a great extent, be reproduced by general surgeons in routine surgical practice.

Anesthesia Recovery Period↗
PubMed2003

Effect of firmness of mattress on chronic non-specific low-back pain: randomised, double-blind, controlled, multicentre trial.

BACKGROUND: A firm mattress is commonly believed to be beneficial for low-back pain, although evidence supporting this recommendation is lacking. We assessed the effect of different firmnesses of mattresses on the clinical course of patients with chronic non-specific low-back pain. METHODS: In a randomised, double-blind, controlled, multicentre trial, we assessed 313 adults who had chronic non-specific low-back pain, but no referred pain, who complained of backache while lying in bed and on rising. Mattress firmness is rated on a scale developed by the European Committee for Standardisation. The H(s) scale starts at 1.0 (firmest) and stops at 10.0 (softest). We randomly assigned participants firm mattresses (H(s)=2.3) or medium-firm mattresses (H(s)=5.6). We did clinical assessments at baseline and at 90 days. Primary endpoints were improvements in pain while lying in bed, pain on rising, and disability. FINDINGS: At 90 days, patients with medium-firm mattresses had better outcomes for pain in bed (odds ratio 2.36 [95% CI 1.13-4.93]), pain on rising (1.93 [0.97-3.86]), and disability (2.10 [1.24-3.56]) than did patients with firm mattresses. Throughout the study period, patients with medium-firm mattresses also had less daytime low-back pain (p=0.059), pain while lying in bed (p=0.064), and pain on rising (p=0.008) than did patients with firm mattresses. INTERPRETATION: A mattress of medium firmness improves pain and disability among patients with chronic non-specific low-back pain.

Adult↗