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Randomised trials represent the 'gold standard' for surgical research and have an important impact on clinical management. We provide an overview of the randomised trials, specifically related to the practice of colorectal surgery that were published between January and December 2003.
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OBJECTIVES: To assess the effectiveness of interventions routinely used in the intensive care management of severe head injury, specifically, the effectiveness of hyperventilation, mannitol, CSF drainage, barbiturates, and corticosteroids. METHODS: Systematic review of all unconfounded randomised trials, published or unpublished, that were available by August 1996. RESULTS: None of the interventions has been reliably shown to reduce death or disability after severe head injury. One trial of hyperventilation was identified of 77 participants. The relative risk for death was 0.73 (95% confidence interval (95% CI) 0.36-1.49), and for death or disability it was 1.14 (95% CI 0.82-1.58). One trial of mannitol was identified of 41 participants. The relative risk for death was 1.75 (95% CI 0.48-6.38), no data were available for disability. No randomised trials of CSF drainage were identified. Two randomised trials of barbiturate therapy were identified, including 126 participants. The pooled relative risk for death was 1.12 (95% CI 0.81-1.54). Disability data were available for one trial. The relative risk for death or disability was 0.96 (95% CI 0.62-1.49). Thirteen randomised trials of corticosteroids were identified, comprising 2073 participants. The pooled relative risk for death was 0.95 (0.84 to 1.07) and for death or disability it was 1.01 (95% CI 0.91 to 1.11). On the basis of the currently available randomised evidence, for every intervention studied it is impossible to refute either a moderate increase or a moderate decrease in the risk of death or disability. CONCLUSION: Existing trials have been too small to support or refute the existence of a real benefit from using hyperventilation, mannitol, CSF drainage, barbiturates, or corticosteroids. Further large scale randomised trials of these interventions are required.
BACKGROUND: Pioglitazone as monotherapy and in combination with sulfonylurea, metformin, or insulin has consistently demonstrated improved glycaemic and lipid parameters in patients with type 2 diabetes mellitus. OBJECTIVE: We performed a subanalysis to examine the effect of pioglitazone on glycaemia and lipids in patients <65 and > or =65 years of age in two double-blind, placebo-controlled monotherapy studies and in three separate multi-centre trials. METHOD: In Study 1, 197 patients were randomised to receive pioglitazone 30 mg/day or placebo for 16 weeks. Study 2 was a forced dose-titration trial in patients randomised to receive pioglitazone 7.5/15/30 mg/day, pioglitazone 15/30/45 mg/day, or placebo daily for 26 weeks. Each of the lower dosages was given for at least 4 weeks and the highest dosage for 16 weeks. The three combination studies evaluated efficacy of pioglitazone 30 or 45 mg/day over a 24-week period in combination with sulfonylureas, metformin, or insulin. RESULTS: In both placebo-controlled monotherapy studies, at 16 weeks, and at maximum pioglitazone dosage, 0.53-0.55% and 0.57-1.27% mean reductions from baseline in glycosylated haemoglobin (HbA(1c)) were seen in patients aged <65 (n = 225) and > or =65 (n = 45) years, respectively. There were statistically significant differences between the placebo and pioglitazone groups in each age cohort. Similar effects were observed in fasting plasma glucose (FPG) levels, with 2.03-2.59 mmol/L and 3.20-4.44 mmol/L mean reductions from baseline, respectively, which were significantly different from the changes in the placebo group, but there was no difference between pioglitazone groups. At treatment endpoint in combination trials, pioglitazone added to sulfonylurea produced a mean decrease in HbA(1c) of 0.78-1.61%, and 1.64-1.96% in patients aged <65 (n = 557) and > or =65 (n = 115) years, respectively. Pioglitazone added to metformin produced a mean decrease in HbA(1c) of 0.78-1.03% and 0.78-0.98% in patients aged <65 (n = 686) and > or =65 (n = 112) years, respectively. Pioglitazone added to insulin produced a mean decrease in HbA(1c) of 1.13-1.37% and 1.39-1.66% in patients aged <65 (n = 500) and > or =65 (n = 156) years, respectively. In patients aged > or =65 years, hypoglycaemia was observed in 1 of 14 patients and in 0 of 13 patients in the two monotherapy studies. In the combination studies, the incidence of hypoglycaemia among patients aged > or =65 years was as follows: 26.7-28.8% combined with sulfonylurea; 0-4.4% combined with metformin; and 53.4-56.4% combined with insulin. CONCLUSION: Pioglitazone monotherapy, or added to a sulfonylurea, metformin, or insulin demonstrated no significant differences in effectiveness while exhibiting similar adverse events in patients aged > or =65 years compared with patients aged <65 years. Well-controlled randomised clinical trials are recommended to confirm the impact of pioglitazone therapy on the glycaemic and lipid control in elderly patients with type 2 diabetes.
When evaluating drug substances, the traditional clinical study setting does not allow scope for observing real-life behaviour since all alternative actions are determined beforehand. However, a study based on prospective or retrospective databases containing real-life data can examine how patients and physicians behave in a real-world setting and can investigate the relationship between the introduction of a drug and the amount of healthcare used in actual practice. We reviewed the quality and potential policy application of published retrospective database studies in which an economic evaluation of the use of drugs in asthma was conducted. A search in literature databases found 16 such studies, which were reviewed and evaluated according to a published checklist. No article fulfilled all the criteria for a 'good' economic evaluation. The results of many of the evaluations may be informative, but not transparent enough to deliver policy conclusions. This may limit the use of the currently published retrospective database studies as a base for policy decision, compared with randomised controlled trials, despite the additional value of these database analyses when well conducted. A greater transparency when presenting material and results is therefore called for, to increase the usefulness of database studies.
Studies on the natural history of endometriosis have demonstrated that the majority of endometriosis implants tend to progress, a finding that indicates eradication of the lesions by medical and/or surgical approaches. Infertility and dysmenorrhea are other indications for medical therapy in this disease. In recent prospective and controlled studies, progestin (at high doses), gestrinone and GnRH agonist analogues have been equally effective as regards elimination of endometriosis and relief of endometriosis-associated symptoms, compared to danazol, a standard treatment in endometriosis. These four classes of drugs differ, however, in their adverse effects and as regards compliance. Danazol is a steroid with androgenic and anabolic effects and it adversely affects lipid metabolism. Gestrinone and 17-OH progestins are weaker, and GnRH agonist analogues and some progestins neutral in these respects. GnRH agonist analogues induce a hypo-estrogenic state with associated climacteric symptoms and mineral loss from the bones. The clinical value of combinations of GnRH analogue and steroid(s), used to prevent these side-effects, is so far unclear. Laparoscopic microsurgery has revolutionized the treatment of endometriosis lesions. Hence, hormone treatment as a supplement to microsurgical approaches may become a dominant form of medical therapy in endometriosis. The definitive value of pre- or post-operative hormonal treatment in this disease should, however, be tested in controlled trials. Such studies have proved antiprostaglandins to be useful in the treatment of dysmenorrhea secondary to endometriosis. Because each of the four drugs was ineffective in the treatment of infertility associated with endometriosis it is a waste of time to expose patients desiring pregnancy to long-term hormonal therapy. Ovarian hyperstimulation with IVF and other methods of assisted fertilisation are promising alternatives, but their definitive value is so far unproven in this disease. Conclusively, the significance of medical therapy in endometriosis is only partly resolved, and therefore, many therapeutic problems await prospective randomised trials and new innovations.
AIMS: To describe the number and type of clinical trials in New Zealand 1998-2003, and to identify the number of trials for which approval was sought in 2003 that were listed with trial registries. METHODS: Annual reports (1998-2003) from all regional ethics committees were reviewed for clinical trials. Trials must have been referred to as phase I, II, or III clinical trials; employ descriptors such as randomised controlled trials or controlled trials; or been known to the authors as randomised controlled trials. Trials registers at ClinicalTrials.gov, Current Controlled Trials, NHMRC Clinical Trials Centre, National Cancer Research Network, CenterWatch, Trans-Tasman Radiation Oncology Group, as well as industry registers were searched using keyword identifiers for the trials submitted for ethical review in 2003. RESULTS: Ethics approval was sought for 665 clinical trials (1998, 118 trials; 1999, 91 trials; 2000, 103 trials; 2001, 104 trials; 2002, 108 trials; 2003, 141 trials). The majority of applications (481, 72%) were submitted to either the Auckland or Canterbury committees. 581 (87%) applications were for phase III trials. 522 (78%) applications were for trials involving pharmacological agents, and 115 applications (17%) were for trials involving procedures, processes, or medical devices. The remaining 28 applications (4%) involved interventions such as diet, complementary therapies, or dental care. Of all applications, 332 (50%) were in the fields of cancer, cardiovascular disease, and respiratory disease. Only 45 (32%) of the 141 trials submitted for review in 2003 were listed in a public domain register. CONCLUSIONS: The number of randomised controlled trials (RCTs) in New Zealand has not clearly increased in recent years despite the greater than ever need for such evidence. Information currently in the public domain could support registers of clinical trials.
Low-dose heparin (L.D.H.) prophylaxis gives good protection against deep venous thrombosis (D.V.T.). In the case of subjects presenting for herniorrhaphy the literature is less unanimous regarding the chance of wound hematoma. In this prospective randomised, matched trial in 86 patients, a wound hematoma incidence of 36 percent was noted in the treatment group as against 7% in the control group. This is statistically significant at the P less than 0.001 level.
BACKGROUND: We investigated the efficacy and cost-effectiveness of five antimicrobial regimens for mild to moderate facial acne and whether propionibacterial antibiotic resistance affects treatment response. METHODS: In this randomised, observer-masked trial, 649 community participants were allocated one of five antibacterial regimens. Primary outcomes were patients' self-assessed improvement and reduction in inflamed lesions at 18 weeks. Analyses were by intention to treat. FINDINGS: Moderate or greater improvement at 18 weeks was reported in 72 (55%) of 131 participants assigned oral oxytetracycline plus topical placebo, 70 (54%) of 130 assigned oral minocycline plus topical placebo, 78 (60%) of 130 assigned topical benzoyl peroxide plus oral placebo, 84 (66%) of 127 assigned topical erythromycin and benzoyl peroxide in a combined formulation plus oral placebo, and 82 (63%) of 131 assigned topical erythromycin and benzoyl peroxide separately plus oral placebo. Most improvement occurred in the first 6 weeks. Treatment differences for the proportion of people with at least moderate improvement were: minocycline versus oxytetracycline -1.2% (unadjusted 95% CI -13.3 to 10.9); combined erythromycin and benzoyl peroxide versus oxytetracycline 11.1% (-0.7 to 22.9) and versus minocycline 12.3% (0.4 to 24.2); erythromycin and benzoyl peroxide separately versus combined formulation -3.5% (-15.2 to 8.2); benzoyl peroxide versus oxytetracycline 5.0% (-7.0 to 17.0), versus minocycline 6.2% (-5.8 to 18.2), and versus combined formulation -6.1% (-17.9 to 5.7). Benzoyl peroxide was the most cost-effective treatment. Efficacy of both tetracyclines was reduced by pre-existing tetracycline resistance. INTERPRETATION: Topical benzoyl peroxide and benzoyl peroxide/erythromycin combinations are similar in efficacy to oral oxytetracycline and minocycline and are not affected by propionibacterial antibiotic resistance.
The meta-analysis of randomised controlled studies (RCS) achieves the highest degree of reliability. Although the status of prospective multicenter clinical trials (PMS) is the subject of controversial discussion, recent publications suggest that these two forms of analysis reveal comparable results. On the other hand, particularly in the operative part of medicine, the problem of recruitment and performing of controlled studies for the more rapid evaluation of new surgical procedures becomes more evident. We followed these two aspects by using a separate analysis of data and biostatistical models. In the evaluation of single aspects, under no circumstances can non-controlled clinical trials replace randomised clinical studies in surgery. Only the use of a variety of forms of analysis in clinical research will lead to the desired scientific findings.
We present the definitions of various types of fracture of the condylar process, which have been adopted for the Strasbourg Osteosynthesis Research Group (SORG), in their Pan-European prospective randomised controlled trial into the management of such fractures. We think that this will assist people in their description of the various types of fracture of the condylar process.
BACKGROUND: Coronary heart disease (CHD) is a major cause of morbidity and mortality in Australia and it is recommended that all persons with unstable angina (UA) or myocardial infarction (MI) participate in secondary prevention as offered in cardiac rehabilitation (CR) programs. However, the majority of patients do not access standard CR and have higher baseline coronary risk and poorer knowledge of CHD than those persons due to commence CR. The objective of this study is to investigate whether a modular guided self-choice approach to secondary prevention improves coronary risk profile and knowledge in patients who do not access standard CR. METHODS/DESIGN: This randomised controlled trial with one year follow-up will be conducted at a tertiary referral hospital. Participants eligible for but not accessing standard CR will be randomly allocated to either a modular or conventional care group. Modular care will involve participation in individualised modules that involve choice, goal-setting and coaching. Conventional care will involve ongoing heart disease management as directed by the participant's doctors. Both modular and conventional groups will be compared with a contemporary reference group of patients attending CR. Outcomes include measured modifiable risk factors, relative heart disease risk and knowledge of risk factors. DISCUSSION: We present the rationale and design of a randomised controlled trial testing a modular approach for the secondary prevention of coronary heart disease following acute coronary syndrome.
BACKGROUND: Trachoma is the world's leading cause of preventable blindness. In 1997 the World Health Organization launched an initiative on trachoma control based on the 'SAFE' strategy (surgery, antibiotics, facial cleanliness and environmental improvement). OBJECTIVES: To assess the evidence supporting the antibiotic arm of the SAFE strategy by assessing the effects of antibiotics on both active trachoma (primary objective) and on Chlamydia trachomatis infection of the conjunctiva (secondary objective). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to February 2005), and EMBASE (1980 to February 2005). We used the Science Citation Index to look for articles that cited the included studies. We searched the reference lists of identified articles and we contacted authors and experts for details of further relevant studies. SELECTION CRITERIA: We included only randomised trials that satisfied either of two criteria: (a) trials in which topical or oral administration of an antibiotic was compared to placebo or no treatment in people with trachoma, (b) trials in which a topical antibiotic was compared with an oral antibiotic in people with trachoma. A subdivision of particular interest was of trials in which topical tetracycline/chlortetracycline was compared with oral azithromycin, as these are the two World Health Organization recommended treatments. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted investigators for missing data. MAIN RESULTS: We found 15 studies that randomised a total of 8678 participants. For both outcomes (active trachoma and laboratory evidence of infection) the results of the chi squared tests suggested that there was significant statistical heterogeneity among the trials. There was also marked clinical heterogeneity. No summary statistics were calculated and we therefore present a narrative summary of the results. For the comparisons of oral or topical antibiotic against placebo/no treatment, the data are consistent with there being no effect of antibiotics but are suggestive of a lowering of the point prevalence of relative risk of both active disease and laboratory evidence of infection at three and 12 months after treatment. For the comparison of oral against topical antibiotics the results suggest that oral treatment is neither more nor less effective than topical treatment. AUTHORS' CONCLUSIONS: There is some evidence that antibiotics reduce active trachoma but results are not consistent and cannot be pooled.
Progress in colorectal surgery over the last few years is evident by the growing number of randomised controlled trials reported. We have scrutinised such trials reported over the last year across the entire spectrum of colorectal disease and have presented the significant findings in this trials report.
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INTRODUCTION: Evidence-based medicine (EBM) has been proposed as a new paradigm of practising medicine. However, an unproductive polarisation between supporters and opponents can make its unbiased assessment difficult. This review gives an overview of the arguments and discusses their surgeon-specific importance. DISCUSSION: As EBM claims a position in the centre of medicine, it borders with other highly debated topics as, for instance, rationing and equity of care, doctor-patient interaction, medical research and education. Most arguments against EBM relate to its role in reducing health expenses by rationing healthcare. We think that the principles of EBM can be applied to make the inevitable process of rationing fair and reproducible. In addition, evidence-based surgery is criticised for interfering with patient individuality and physician autonomy, although this is a misunderstanding. Furthermore, the evidence-basis of EBM, in particular the randomised controlled trial (RCT) and systematic review, has been subject of discussion. Additionally, surgical research has its own inherent difficulties and, ultimately, some clinicians have doubted the practical feasibility of applying EBM at the bedside, because searching and critically appraising the literature is too difficult and time consuming. CONCLUSIONS: We believe that most critics consider EBM to be a potentially dangerous tool, because they fear it will be used against themselves. Thus, these conflicts only prove that EBM as a methodology may have a strong impact on solving them. As EBM has already made discernible progress, surgeons should not stand aside from these activities, which are bound to strongly influence healthcare in the next century.
BACKGROUND: About 350 million people are chronically infected carriers of hepatitis B virus and are at a higher risk of serious illness and death from cirrhosis of the liver and liver cancer. Chinese medicinal herbs have been used widely for more than 2000 years to treat chronic liver disease. OBJECTIVES: To assess whether Chinese medicinal herbs are effective and safe for treating asymptomatic carriers of hepatitis B virus. SEARCH STRATEGY: The trials registers of the Cochrane Hepato-Biliary Group, the Cochrane Library and the Cochrane Complementary Medicine Field were searched in combination with MEDLINE, EMBASE, and handsearches of Chinese journals and conference proceedings. SELECTION CRITERIA: Randomised or quasi-randomised trials (minimum follow-up three months) in asymptomatic carriers of hepatitis B virus. Chinese medicinal herbs (single herb or compound of herbs) compared with placebo, no intervention, general non-specific treatment, or interferon treatment. Trials of Chinese medicinal herbs plus interferon versus interferon alone were also included. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers. Analysis was performed by intention-to-treat where possible. Pre-specified subgroup analyses were: ethnic origin, age at time of infection, and single herb or compound of herbs. MAIN RESULTS: Three randomised clinical trials (307 patients) that followed patients for three months or more after the end of treatment were included. The methodological quality was poor. The herbal compound 'Jianpi Wenshen recipe' had significant effects on viral markers compared to interferon: relative risk 2.40 (95% CI 1.01 to 5.72) for clearance of serum HBsAg, 2.03 (95% CI 0.98 to 4.20) for clearance of HBeAg, and 2.54 (95% CI 1.13 to 5.70) for seroconversion of HBeAg to anti-HBe. Phyllanthus amarus and Astragalus membranaceus showed no significant antiviral effect compared with placebo. Analysis of pooling eight randomised clinical trials with less than three months follow-up did not show a significant benefit of Chinese medicinal herbs on viral markers. Data on long-term clinical outcomes and quality of life were lacking. REVIEWER'S CONCLUSIONS: Based on one low quality trial, the medicinal herb 'Jianpi Wenshen recipe' may have an antiviral activity in asymptomatic carriers of hepatitis B virus. However, rigorous randomised, double-blind, placebo-controlled trials are needed before herbs should be used for this condition.
BACKGROUND: Hypothermia incurred during routine postnatal resuscitation is a world-wide issue (across all climates), with associated morbidity and mortality. Keeping vulnerable preterm infants warm is problematic even when recommended routine thermal care guidelines are followed in the delivery suite. OBJECTIVES: To assess efficacy and safety of interventions, designed for prevention of hypothermia in preterm and/or low birthweight infants, applied within 10 minutes after birth in the delivery suite compared with routine thermal care. SEARCH STRATEGY: The standard search strategy of The Cochrane Collaboration was followed. Electronic databases were searched: MEDLINE (1966 to May Week 4 2004 ), CINAHL (1982 to May Week 4 2004), EMBASE (1974 to 09/07/04), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2004), Database of Abstracts of Reviews of Effects (DARE 1994 to July 2004), conference/symposia proceedings using ZETOC (1993 to July 2004), ISI proceedings (1990 to 09/07/2004) and OCLC WorldCat (July 2004). Identified articles were cross-referenced. No language restrictions were imposed. SELECTION CRITERIA: All trials using randomised or quasi-randomised allocations to test a specific intervention designed to prevent hypothermia, (apart from 'routine' thermal care) applied within 10 minutes after birth in the delivery suite to infants of < 37 weeks' gestational age or birthweight </=2500 g. DATA COLLECTION AND ANALYSIS: Methodological quality was assessed and data were extracted for important clinical outcomes including adverse effects of the intervention by at least three independent reviewers. Authors were contacted for missing data. Data were analysed using RevMan 4.2.5. Relative risk (RR), risk difference (RD) and number needed to treat (NNT) with 95% confidence limits were calculated for each dichotomous outcome and mean differences (MD) with 95% confidence limits for continuous outcomes. MAIN RESULTS: Six studies giving a total of 304 infants randomised and 295 completing the studies were included. Four comparisons to 'routine care' were undertaken within two categories: 1) barriers to heat loss (four studies): plastic wrap or bag (three), stockinet caps (one) and 2) external heat sources (two studies): skin-to-skin (one), transwarmer mattress (one). Plastic barriers were effective in reducing heat losses in infants < 28 weeks' gestation (three studies, n = 159; WMD 0.76 degrees C; 95% CI 0.49, 1.03) but not in the 28 to 31 week group. There was insufficient evidence to suggest that plastic wrap reduces the risk of death within hospital stay (three studies, n = 161; typical RR 0.63; 95% CI 0.32, 1.22; typical RD -0.09; 95% CI -0.20, 0.03). There was no evidence of a significant difference in major brain injury, mean duration of oxygen therapy or hospitalisation for infants < 29 weeks' gestation. Stockinet caps were not effective (borderline significant for infants < 2000 g birthweight) in reducing heat losses.Skin-to-skin care was shown to be effective in reducing the risk of hypothermia when compared to conventional incubator care for infants 1200 to 2199 g birthweight (one study, n = 31; RR 0.09; 95% CI 0.01, 0.64; NNT 2; 2 to 4). The transwarmer mattress significantly kept infants </=1500 g warmer and reduced the incidence of hypothermia on admission to NICU (one study, n = 24; RR 0.30; 95% CI 0.11, 0.83; NNT 2 range 2 to 4). AUTHORS' CONCLUSIONS: Plastic wraps or bags, skin-to-skin care and transwarmer mattresses all keep preterm infants warmer, leading to higher temperatures on admission to neonatal units and less hypothermia. Given the low NNT, consideration should be given to using these interventions in the delivery suite. However, the small numbers of infants and studies and the absence of long term follow-up mean that firm recommendations for clinical practice cannot be given. There is a need to conduct large, high quality randomised controlled trials looking at long-term outcomes.