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Psychological debriefing: controversy and challenge.

OBJECTIVE: The efficacy of psychological debriefing following potentially traumatising events has become extremely controversial. This review aims to identify the issues underlying this controversy and their theoretical, social and political ramifications which are important in other areas of psychiatry and the social sciences. METHOD: The historical background to the debriefing debate and the (largely negative) results of recent randomised controlled trials (RCTs) are reviewed. RESULTS: Despite the negative results of recent RCTs, psychological debriefing remains the most widely used structured intervention following potentially traumatising events, designed to reduce the incidence of long-term psychiatric morbidity. The clinical relevance these trials and their applicability in vivo is questioned. There are implicit difficulties in conducting rigorous randomised controlled trials of group debriefing, and such trials may be unachievable. CONCLUSIONS: Demonstrating the efficacy of debriefing or other preventive interventions presents major challenges to investigators and it is unlikely the controversy will be resolved in the near future.

Crisis Intervention↗

Selective serotonin reuptake inhibitors versus tricyclic and heterocyclic antidepressants: comparison of drug adherence.

BACKGROUND: Selective serotonin reuptake inhibitors are thought to have better discontinuation rates (i.e. less people dropping out) than tricyclic and heterocyclic antidepressant drugs. It is important to quantify the drop-out rates of different antidepressant drugs in order to have a better understanding of the relative tolerability of these drugs. OBJECTIVES: To assess the comparative tolerability of selective serotonin reuptake inhibitors and tricyclic/heterocyclic antidepressant drugs. SEARCH STRATEGY: We searched the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Registers (1997 to 1999), MEDLINE (1966 to 1999), EMBASE (1974 to 1999) We also searched specialist journals, the reference lists of relevant papers and previous systematic reviews, conference abstracts and government documents. Representatives of the pharmaceutical industry were contacted. SELECTION CRITERIA: Parallel group randomised controlled trials comparing selective serotonin reuptake inhibitors with tricyclic or heterocyclic antidepressants in people with depression. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and a third reviewer checked any cases of disagreement. MAIN RESULTS: We included 136 trials. The selective serotonin reuptake inhibitors showed less participants dropping out compared to the tricyclic/heterocyclic group (odds ratio 1.21, 95% confidence interval 1.12 to 1.30). A statistically significant difference was found in total drop-outs between the selective serotonin reuptake inhibitors and the old tricyclics as well as the newer tricyclics. When the selective serotonin reuptake inhibitors were compared to the heterocyclic antidepressants, there was a non significant difference favouring the selective serotonin reuptake inhibitors. The poor tolerability profile of the old tricyclics was explained by differences in drop-outs for side-effects, but not for inefficacy. REVIEWER'S CONCLUSIONS: Whilst selective serotonin reuptake inhibitors do appear to show an advantage over tricyclic drugs in terms of total drop-outs, this advantage is relatively modest. This has implications for pharmaco-economic models, some of which may have overestimated the difference of drop-out rates between selective serotonin reuptake inhibitors and tricyclic antdepressants. These results are based on short-term randomised controlled trials, and may not generalise into clinical practice.

Antidepressive Agents↗

Strategies for managing sexual dysfunction induced by antidepressant medication.

BACKGROUND: Sexual dysfunction (including altered desire, orgasmic dysfunction, erectile and ejaculatory problems) is a relatively common side effect of antidepressant medication. These sexual side effects may compromise a person's lifestyle and result in a lack of compliance with the prescribed antidepressant to the detriment of the person's mental health. OBJECTIVES: The objective of this review was to assess the effectiveness of management strategies for sexual dysfunction caused by antidepressant medication. SEARCH STRATEGY: We searched the CCDANCTR (March 2003), the Cochrane Central Register of Controlled Trials (Cochrane Library issue 2, 2004), MEDLINE (1966 - June 2004), EMBASE (1980 - March 2004), CINAHL (1982 - March 2004), PsycINFO (1984 - March 2004) and the reference lists of articles. We also contacted pharmaceutical companies and experts in the field of sexology. SELECTION CRITERIA: Randomised controlled trials comparing the management strategies for antidepressant induced sexual dysfunction were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Study authors were contacted for additional information. Adverse effect information was collected from the trials. MAIN RESULTS: Fifteen trials involving 904 people were included. One trial involving 75 people with sexual dysfunction due to sertraline assessed changing antidepressant. Switching to nefazodone was significantly less likely to result in the re-emergence of sexual dysfunction than restarting sertraline (RR 0.34, 95% CI 0.15 - 0.6) and was not associated with any worsening of depression. Fourteen trials involving 829 people assessed the addition of other medication while continuing the same antidepressant. Meta-analysis of two trials involving 113 men with erectile dysfunction found that the addition of sildenafil resulted in less sexual dysfunction at endpoint on rating scales including the International Index of Erectile Function (IIEF; WMD 19.36, 95% CI 15.00 to 23.72). There was no significant difference in dropout rates between sildenafil and placebo. One trial found the addition of bupropion led to improved scores on the Changes in Sexual Functioning Questionnaire desire-frequency subscale (WMD 0.88, 95% CI 0.21 - 1.55). One trial found that the addition of tadalafil was associated with greater improvement in the erectile function domain of the IIEF than placebo (WMD 8.10; 95% CI 4.62 to 11.68). Other augmentation strategies failed to show statistically significant improvements in sexual dysfunction compared with placebo. REVIEWERS' CONCLUSIONS: The currently available evidence is rather limited, with small numbers of trials assessing each strategy. However, while further randomised data is awaited, for men with antidepressant-induced erectile dysfunction, the addition of sildenafil appears to be an effective strategy.

Antidepressive Agents↗

Steroids for idiopathic sudden sensorineural hearing loss.

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSHL) is a clinical diagnosis characterised by a sudden deafness of cochlear or retrocochlear origin in the absence of a clear precipitating cause. Steroids are commonly prescribed to treat this condition. There is no consensus on their effectiveness. OBJECTIVES: To determine the effectiveness and the side-effect profile of steroids in the treatment of idiopathic sudden sensorineural hearing loss. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to December 2004) and EMBASE (1974 to December 2004). Reference lists of all trials were also manually searched. SELECTION CRITERIA: We identified all randomised controlled trials (with or without blinding) in which steroids were evaluated in comparison with either no treatment or a placebo. Trials including the use of steroids in combination with another treatment were considered if the comparison control group also received the same other treatment. The full text articles of all the retrieved trials of possible relevance were reviewed by the two authors and the inclusion criteria applied independently. Any differences in opinion about which studies to include in the reviews were resolved by discussion. DATA COLLECTION AND ANALYSIS: Trials were graded for methodological quality using the Cochrane approach. The data extraction was performed in a standardised manner by one author and rechecked by the other author, and where necessary investigators were contacted to obtain the missing information. Meta-analysis was neither possible nor considered appropriate because of the heterogeneity of the populations studied, the differences in steroid formulations, dosages and duration of the treatment. The quality of the result of each study was analysed and reported individually. A narrative overview of the result is presented. MAIN RESULTS: Only two trials satisfied the inclusion criteria and both were of low methodological quality. One trial showed a lack of effect of oral steroids in hearing improvement compared with the placebo control group. The other trial showed a significant improvement of hearing in 61% of the patients receiving oral steroid and in only 32% of the patients from the control group (combination of placebo treated group and untreated control group). There was no clear evidence presented in the former study about any harmful side effects of the steroids. The latter study declared that no patients suffered from adverse effects from the steroid treatment. AUTHORS' CONCLUSIONS: The value of steroids in the treatment of idiopathic sudden sensorineural hearing loss remains unclear since the evidence obtained from randomised controlled trials are contradictory in outcome, in part because the studies are based upon too small a number of patients.

Anti-Inflammatory Agents↗

Hyperbaric oxygen therapy for thermal burns.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) consists of intermittently administering 100% oxygen at pressures greater than 1 atmosphere in a pressure vessel. This technology has been used to treat a variety of disease states and has been described as helping patients who have sustained burns. OBJECTIVES: The aim of this review was to assess the evidence for the benefit of hyperbaric oxygen treatment (HBOT) for the treatment of thermal burns. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002), MEDLINE (Ovid 1966 to November Week 2, 2003), CINAHL (Ovid 1982 to December Week 2 2003), EMBASE (Ovid 1980 to September 2003), DORCTHIM (Database of Randomised Controlled Trials in Hyperbaric Medicine) from inception to 2003, and reference lists of articles. SELECTION CRITERIA: We included all randomised controlled trials that compared the effect of HBOT with no HBOT (no treatment or sham). DATA COLLECTION AND ANALYSIS: Two authors using standardised forms extracted the data independently. Each trial was assessed for internal validity with differences resolved by discussion. Data was extracted and entered into RevMan 4.2.3. MAIN RESULTS: Four randomised controlled trials were identified, of which two satisfied the inclusion criteria. The trials were of poor methodological quality. As a result, it was difficult to have confidence in the individual results and it would not have been appropriate to attempt to pool the data. One trial reported no difference in length of stay, mortality, or number of surgeries between the control and HBO-treated groups once these variables were adjusted for the patient's condition. The second trial reported mean healing times that were shorter in patients exposed to HBOT (mean: 19.7 days versus 43.8 days). REVIEWERS' CONCLUSIONS: This systematic review has not found sufficient evidence to support or refute the effectiveness of HBOT for the management of thermal burns. Evidence from the two randomised controlled trials is insufficient to provide clear guidelines for practice. Further research is needed to better define the role of HBOT in the treatment of thermal burns.

Burns↗

Randomised controlled trial of treatment of chronic suppurative otitis media in Kenyan schoolchildren.

BACKGROUND: The outcomes of treatment of chronic suppurative otitis media (CSOM) are disappointing and uncertain, especially in developing countries. Because CSOM is the commonest cause of hearing impairment in children in these countries, an effective method of management that can be implemented on a wide scale is needed. We report a randomised, controlled trial of treatment of CSOM among children in Kenya; unaffected schoolchildren were taught to administer the interventions. METHODS: We enrolled 524 children with CSOM, aged 5-15 years, from 145 primary schools in Kiambu district of Kenya. The schools were randomly assigned treatments in clusters of five in a ratio of two to dry mopping alone (201 children), two to dry mopping with topical and systemic antibiotics and topical steroids (221 children), and one to no specific treatment (102 children). Schools were matched on factors thought to be related to their socioeconomic status. The primary outcome measures were resolution of otorrhoea and healing of tympanic membranes on otoscopy by 8, 12, and 16 weeks after induction. Absence of perforation was confirmed by tympanometry, and hearing levels were assessed by audiometry. 29 children were withdrawn from the trial because they took non-trial antibiotics. There was no evidence of differences in timing of withdrawals between the groups. FINDINGS: By the 16-week follow-up visit, otorrhoea had resolved in a weighted mean proportion of 51% (95% CI 42-59) of children who received dry mopping with antibiotics, compared with 22% (14-31) of those who received dry mopping alone and 22% (9-35) of controls. Similar differences were recorded by the 8-week and 12-week visits. The weighted mean proportions of children with healing of the tympanic membranes by 16 weeks were 15% (10-21) in the dry-mopping plus antibiotics group, 13% (5-20) in the dry-mopping alone group, and 13% (3-23) in the control group. The proportion with resolution in the dry-mopping alone group did not differ significantly from that in the control group at any time. Hearing thresholds were significantly better for children with no otorrhoea at 16 weeks than for those who had otorrhoea, and were also significantly better for those whose ears had healed than for those with otorrhoea at all times. INTERPRETATION: Our finding that dry mopping plus topical and systemic antibiotics is superior to dry mopping alone contrasts with that of the only previous community-based trial in a developing country, though it accords with findings of most other trials in developed countries. The potential role of antibiotics needs further investigation. Further, similar trials are needed to identify the most cost-effective and appropriate treatment regimen for CSOM in children in developing countries.

Administration, Topical↗

[Indications for revascularisation of a carotid stenosis].

TO PREVENT ISCHEMIC STROKE: Three types of measures should be taken: correction of the vascular risk factors, administration of antithrombotic agents and carotid revascularisation in patients selected on the basis of clinical and imaging criteria. CAROTID REVASCULARISATION MEASURES: The optimal indications are carotid surgery for severe symptomatic stenosis, while the benefits are marginal in severe asymptomatic stenosis and in moderate symptomatic stenosis. INDICATIONS FOR PERCUTANEOUS ANGIOPLASTY WITH PLACING OF AN ENDOPROSTHESIS: Angioplasty with endoprosthesis, a possible alternative to surgery, must be restricted to symptomatic stenosis either in randomised studies or in severe stenosis in patients in whom surgery is technically contraindicated.

Angioplasty, Balloon↗

Blinding and exclusions after allocation in randomised controlled trials: survey of published parallel group trials in obstetrics and gynaecology.

OBJECTIVE: To assess the methodological quality of approaches to blind ing and to handling of exclusions as reported in randomised trials from one medical specialty. DESIGN: Survey of published, parallel group randomised controlled trials. DATA SOURCES: A random sample of 110 reports in which allocation was described as randomised from 1990 and 1991 volumes of four journals of obstetrics and gynaecology. MAIN OUTCOME MEASURES: The adequacy of the descriptions of double blinding and exclusions after randomisation. RESULTS: Through 31 trials reported being double blind, about twice as many could have been. Of the 31 trials only eight (26%) provided information on the protection of the allocation schedule and only five (16%) provided some written assurance of successful implementation of double blinding. Of 38 trials in which the authors provided sufficient information for readers to infer that no exclusions after randomisation had occurred, six (16%) reported adequate allocation concealment and none stated that an intention to treat analysis had been performed. That compared with 14 (27%) and six (12%), respectively, for the 52 trials that reported exclusions. CONCLUSIONS: Investigators could have double blinded more often. When they did double blind, they reported poorly and rarely evaluated it. Paradoxically, trials that reported exclusions seemed generally of a higher methodological standard than those that had no apparent exclusions. Exclusions from analysis may have been made in some of the trials in which no exclusions were reported. Editors and readers of reports of randomised trials should understand that flawed reporting of exclusions may often provide a misleading impression of the quality of the trial.

Double-Blind Method↗

Systematic review of efficacy of topical rubefacients containing salicylates for the treatment of acute and chronic pain.

OBJECTIVE: To determine the efficacy and safety of topical rubefacients containing salicylates in acute and chronic pain. DATA SOURCES: Electronic databases and manufacturers of salicylates. STUDY SELECTION: Randomised double blind trials comparing topical rubefacients with placebo or another active treatment, in adults with acute or chronic pain, and reporting dichotomous information, around a 50% reduction in pain, and analyses at one week for acute conditions and two weeks for chronic conditions. DATA EXTRACTION: Relative benefit and number needed to treat, analysis of adverse events, and withdrawals. DATA SYNTHESIS: Three double blind placebo controlled trials had information on 182 patients with acute conditions. Topical salicylate was significantly better than placebo (relative benefit 3.6, 95% confidence interval 2.4 to 5.6; number needed to treat 2.1, 1.7 to 2.8). Six double blind placebo controlled trials had information on 429 patients with chronic conditions. Topical salicylate was significantly better than placebo (relative benefit 1.5, 1.3 to 1.9; number needed to treat 5.3, 3.6 to 10.2), but larger, more valid studies were without significant effect. Local adverse events and withdrawals were generally rare in trials that reported them. CONCLUSIONS: Based on limited information, topically applied rubefacients containing salicylates may be efficacious in the treatment of acute pain. Trials of musculoskeletal and arthritic pain suggested moderate to poor efficacy. Adverse events were rare in studies of acute pain and poorly reported in those of chronic pain. Efficacy estimates for rubefacients are unreliable owing to a lack of good clinical trials.

Acute Disease↗

Surfactant therapy for meconium aspiration syndrome: current status.

Meconium aspiration syndrome (MAS) is an important cause of respiratory distress in the term infant. Therapy for the disease remains problematic, and newer treatments such as high-frequency ventilation and inhaled nitric oxide are being applied with increasing frequency. There is a significant disturbance of the pulmonary surfactant system in MAS, with a wealth of experimental data indicating that inhibition of surfactant function in the alveolar space is an important element of the pathophysiology of the disease. This inhibition may be mediated by meconium, plasma proteins, haemoglobin and oedema fluid, and, at least in vitro, can be overcome by increasing surfactant phospholipid concentration. These observations have served as the rationale for administration of exogenous surfactant preparations in MAS, initially as standard bolus therapy and, more recently, in association with therapeutic lung lavage. Bolus surfactant therapy in ventilated infants with MAS has been found to improve oxygenation in most studies, although there are a significant proportion of nonresponders and in many cases the effect is transient. Pooled data from randomised controlled trials of surfactant therapy suggest a benefit in terms of a reduction in the requirement for extracorporeal membrane oxygenation (relative risk 0.48 in surfactant-treated infants) but no diminution of air leak or ventilator days. Current evidence would support the use of bolus surfactant therapy on a case by case basis in nurseries with a relatively high mortality associated with MAS, or the lack of availability of other forms of respiratory support such as high-frequency ventilation or nitric oxide. If used, bolus surfactant should be administered as early as practicable to infants who exhibit significant parenchymal disease, at a phospholipid dose of at least 100 mg/kg, rapidly instilled into the trachea. Natural surfactant or a third-generation synthetic surfactant should be used and the dosage repeated every 6 hours until oxygenation has improved. Lung lavage with dilute surfactant has recently emerged as an alternative to bolus therapy in MAS, which has the advantage of removing surfactant inhibitors from the alveolar space in addition to augmenting surfactant phospholipid concentration. Combined animal and human data suggest that lung lavage can remove significant amounts of meconium and alveolar debris, and thereby improve oxygenation and pulmonary mechanics. Arterial oxygen saturation inevitably falls during lavage but has been noted to recover relatively rapidly, even in infants with severe disease. Several randomised controlled trials of surfactant lavage in MAS are underway, and until the results are known, lavage must be considered an unproven and experimental therapy.

Animals↗

Chiropractic manipulation for non-spinal pain--a systematic review.

AIMS: Chiropractic manipulation is mostly used for spinal problems but, in an increasing number of cases, also for non-spinal conditions. This systematic review is aimed at critically evaluating the evidence for or against the effectiveness of this approach. METHODS: Five electronic databases were searched for all randomised clinical trials of chiropractic manipulation as a treatment of non-spinal pain. They were evaluated according to standardised criteria. RESULTS: Eight such studies were identified. They related to the following conditions: fibromyalgia, carpal tunnel syndrome, infantile colic, otitis media, dysmenorrhoea and chronic pelvic pain. Their methodological quality ranged from mostly poor to excellent. Their findings do not demonstrate that chiropractic manipulation is an effective therapy for any of these conditions. CONCLUSIONS: Only very few randomised clinical trials of chiropractic manipulation as a treatment of non-spinal conditions exist. The claim that this approach is effective for such conditions is not based on data from rigorous clinical trials.

Humans↗

Nifedipine and acebutolol in combination for the treatment of moderate to severe essential hypertension.

In a randomised, crossover study of patients with moderate to severe essential hypertension, the effects of the calcium entry antagonist nifedipine and the beta-receptor blocking drug acebutolol were studied on their own, and in combination. After 4 weeks of nifedipine tablets 20 mg twice daily (Adalat, Bayer), mean supine blood pressure (BP) fell by 20 mmHg and after 4 weeks of acebutolol 200 mg twice a day (Sectral, May & Baker) by 11 mmHg. When nifedipine and acebutolol were given in combination in the above doses for 4 weeks, there was a significantly greater fall in BP than with either agent alone, supine mean arterial pressure falling by 27 mmHg. The above BPs were measured 2 h after the last dose of tablets. Measurements 12 h after the last dose showed smaller falls in BP, with a significantly greater fall with combination treatment than with acebutolol alone. The fall in BP 12 h after the last dose of the combination was greater than with nifedipine alone but this difference was not statistically significant. This randomised, controlled study showed that nifedipine and acebutolol have a marked additive effect on BP which is sustained for at least 12 h after treatment.

Acebutolol↗

[The request for consent in clinical research: a randomized study in healthy subjects].

To compare two strategies of consent requirement (classical informed consent and randomised consent according to Zelen), the Clinical Data Elaboration Centre of South Italy, within the special project Clinical Application of Oncological Research of the National Research Council of Italy (CNR-ACRO) invited healthy people visiting the 7th edition of the scientific exhibition "Futuro Remoto" to simulate of being ill and receiving the offer of entering a clinical trial. Within informed consent strategy patients are asked to agree to the randomisation process, while, in the randomised consent, randomised treatment assignment is performed before consent requirement and patients should agree directly to the assigned therapy. Major aims of the study were (a) to compare the strategies in terms of refusal rate to a hypothetical clinical trial, and (b) to estimate whether severity of prognosis affected subjects' decision. 3,217 visiting people participated to the simulation; they were prevalently young, males and with a high level of school education. The study was performed in two different scenarios. In the first one, with one choice option, subject refusing consent could receive standard therapy only; refusal rate was 16% after informed consent and 13.4% after randomised consent (for experimental therapy). In the other scenario, with two choice options, subjects refusing consent could choose the preferred therapy; refusal rate was 20.6% after informed consent, 48.1% after randomised consent (for standard therapy) and 13.4% after randomised consent (for experimental therapy).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Interactions between radiation and hormonal therapy in breast cancer: simultaneous or sequential treatment].

BACKGROUND: Combining radiation and hormone therapy (administration of selective estrogen receptor modulators) has become common clinical practice in recent years for receptor positive breast cancer. Little is known about a possible interaction of both treatment modalities if they are given simultaneously. Tamoxifen (antiestrogen molecule, triphenylethylene derivative) may theoretically render cancer cells less responsive to radiotherapy arresting hormone-receptor-positive cells in G0/G1 phase and increase the risk of breast and lung fibrosis stimulating the secretion of transforming growth factor beta in human fibroblasts. PURPOSE: This article reviews the published data to assess the impact of sequencing of hormonal and radiation therapy on outcomes in breast cancer. METHODS: Computerised searches for publications debating the sequencing of hormonal therapy relative to radiation therapy were done using MEDLINE data. RESULTS: Results of tamoxifen experiments with cell culture regarding radioprotection of tumour clonogens are conflicting. In contrast to in vitro results, in animal studies no protective effect of tamoxifen was observed. In one in vitro study, letrozole (non-steroid selective aromatase inhibitor) had a radiosensitizing effect on breast-cancer lines. No randomised clinical trials to date have studied sequencing of tamoxifen or other selective estrogen receptor modulators and radiotherapy. Results from retrospective clinical studies which included treatment arms with and without tamoxifen showed reduction in tumour recurrence with tamoxifen. Some of these studies have noted increased risk of lung and breast fibrosis with tamoxifen with radiotherapy. Results of three articles examined the effect of tamoxifen sequence showed no adverse effect on local control or survival in sequential versus concurrent tamoxifen and radiation patients. One of the three studies also assessed the risk of complications with respect to the timing of tamoxifen with radiotherapy. There was no difference in the rates of complications between the two groups. The association of radiation and selective aromatase inhibitors or aromatase inactivators has not been addressed in clinical studies. CONCLUSIONS: Combined application of tamoxifen and radiotherapy improves survival and local control in breast cancer. Available clinical studies do not indicate that the simultaneous application of tamoxifen and radiotherapy is disadvantageous, as was suggested by some of the in vitro studies. The risk of subcutaneous breast and lung fibrosis might be slightly increased if tamoxifen is given simultaneously with radiotherapy. Both treatment modalities should be started early after surgery. There is no sufficient evidence to withhold tamoxifen administration during irradiation of breast cancer. The issue of optimal sequencing of hormonal and radiotherapy should be addressed in randomised clinical trials.

Animals↗

[Chemoradiotherapy and anal canal cancer].

Local control and sphincter preservation are the two challenges of anal canal cancer treatment. These tumors are radio- and chemo-sensitive and treatment moved from surgical approach, with abdominoperineal resection, to definitive radiation therapy with or without concurrent chemotherapy. Randomised trials proved the benefit of combined modality with chemoradiotherapy and of mitomycine C (MMC) compared with radiotherapy alone, with a toxic death rate of about 2%. Indications of chemoradiotherapy are locally advanced tumor T2 > or = 4 cm, T3-4 or N1-3 but the best modalities of combined treatment are still under debate. Standard chemotherapy is 5 flurouracile (5FU) + MMC, but cisplatinum (CDDP) is an effective and well tolerated substitute for MMC. Favourable results with CDDP-containing regimen in term of toxicity and carcinologic control have been reported in phase II and retrospective studies. Total radiation dose, overall duration of radiation therapy, duration of the gap and indications of additional boost are not clear, but it is demonstrated that overall duration of treatment should be as short as possible to improve the therapeutic radio. Phase II and III studies are ongoing, to evaluate the best chemotherapy regimen between 5FU+MMC and 5FU+CDDP, the benefit of neoadjuvant or maintenance chemotherapy and the interest of increased total dose. Next future could be the utilisation of oral 5FU. This article is a review of past randomised trials, phases II and retrospective study on radiochemotherapy of anal canal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

[Calcaneal fractures--the most frequent tarsal fractures].

Operative treatment of intra-articular calcaneal fractures with anatomical reduction and early mobilisation has lead to a considerable improvement of the functional results of these severe injuries over the recent two decades. New tendencies like modified approaches tailored according to the vascular anatomy, arthroscopic control of joint reduction in conjunction with open or percutaneous procedures, early flap coverage for severe open fractures or closed fractures with full thickness skin necrosis, the use of interlocking plates that further minimises the need of bone grafting and subtalar arthrolysis at the time of hardware removal for fibrous overgrowth have the potential for further improvement of the outcome. The observation from several comparative studies that operative treatment leads to superior results in displaced intra-articular calcaneal fractures has been qualified in a recent prospective, randomised multicentre trial. This paper presents and the authors' experience with the demanding operative treatment of these fractures together with new developments aiming at improving the clinical results.

Arthroscopy↗