The objective of this study was to assess the evidence for or against the effectiveness of cupping as a treatment option for pain. Fourteen databases were searched. Randomized clinical trials (RCTs) testing cupping in patients with pain of any origin were considered. Trials using cupping with or without drawing blood were included, while trials comparing cupping with other treatments of unproven efficacy were excluded. Trials with cupping as concomitant treatment together with other treatments of unproven efficacy were excluded. Trials were also excluded if pain was not a central symptom of the condition. The selection of studies, data extraction and validation were performed independently by three reviewers. Seven RCTs met all the inclusion criteria. Two RCTs suggested significant pain reduction for cupping in low back pain compared with usual care (P < 0.01) and analgesia (P < 0.001). Another two RCTs also showed positive effects of cupping in cancer pain (P < 0.05) and trigeminal neuralgia (P < 0.01) compared with anticancer drugs and analgesics, respectively. Two RCTs reported favorable effects of cupping on pain in brachialgia compared with usual care (P = 0.03) or heat pad (P < 0.001). The other RCT failed to show superior effects of cupping on pain in herpes zoster compared with anti-viral medication (P = 0.065). Currently there are few RCTs testing the effectiveness of cupping in the management of pain. Most of the existing trials are of poor quality. Therefore, more rigorous studies are required before the effectiveness of cupping for the treatment of pain can be determined.

Projective and reflex zones of inner organs to the body's surface are well described but there are only few clinical studies about abnormal zones. OBJECTIVE: The aim of our study was to investigate associations between chronic irritation of tonsils, abnormalities of the connective tissue areas over the musculus trapezius and the severity of brachialgia paresthetica nocturna. METHODS: Cross sectional study in 100 adult pain patients from an outpatient pain department. Patients with tonsillectomy were excluded. Examinations of tonsils and the connective tissue area were done separately by two mutually blinded physicians. Both were also blinded to the patients' evaluation of his/her brachialgia. RESULTS: Regardless of the lateralization, the severity of the tonsil irritations was correlated with the abnormalities of the connective tissue areas (Spearman's rho = 0.82; 95% confidence interval (CI): 0.74-0.87; p < 0.001) and the severity of the brachialgia (rho = 0.64, CI: 0.50-0.74; p < 0.001), furthermore indurations of connective tissue areas correlated with the severity of brachialgia homolaterally (rho = 0.57; CI: 0.42-0.69; p < 0.001). These correlations are considerably higher than those of other connective tissue areas. CONCLUSIONS: The results support the existence of easy to diagnose reflex zones, at least in a highly selected population of pain patients. They can give plausible hints for naturopathic treatments of brachialgia paresthetica nocturna, i.e. treatment of the relevant connective tissue zone above the M. trapezius.

PURPOSE: Surrogate models have been postulated for (re-)registration of external remedies for pain, whose active substances are in accordance to monographs. In a new human model, we investigated an ointment consisting of high dosed herbal ingredients. METHODS: We conducted a clinical study in 32 healthy volunteers. Four muscle regions were treated with the ointments (verum on the one side and placebo on the other) in a randomized and doubleblinded manner immediately after a standardized physical exercise with individual intensity, as well as after 1, 2 and 24 h. Acute muscle pain and muscle tension for each region was documented repeatedly during the following two days by visual analogue scale (VAS). Primary outcome parameter was the difference of pain during the follow up given as area under the curve (AUC) of VAS for corresponding right and left regions, treated with verum or placebo. Also the difference of muscle tension was documented and evaluated in an analogous way. RESULTS: 30 out of 32 included patients finished the study, but developed only moderate muscle pain, with highest pain scores for extension muscles of the arm. There was less pain in the course for the verum in 3 of the 4 regions, the mean difference of individual AUCs was at highest for the extension (triceps) muscles of the arm, but between-group differences failed significance. Feeling of muscle tension was higher than that of pain, with smaller mean AUCs of verum in all 4 regions; the differences were significant in total (p<0.02) and in 2 of 4 single regions. CONCLUSIONS: Physical exercise was not intensive enough to exert clear symptoms. Our volunteers with sportive background seem not to show severe symptoms of muscle pain and muscle tension even after an intensive training. Despite low levels of symptoms, verum showed better courses of muscle tension and muscle pain. For future studies it seems better not to use volunteers with sportive background but totally untrained persons in order to achieve pronounced symptoms. The model is feasible, sensitive, inexpensive and is much more clinically relevant than those, focusing on perfusion parameters of skin.

Malignant ascites is a frequent complication in oncological diseases. There are no standard therapies for any primary tumour. We report the case of a woman, aged 49 years at the time of primary diagnosis, who suffered from recurrent ascites resulting from liver metastasis of breast cancer. Based on the literature and former experience of our department, mistletoe extract was repeatedly applied intraperitoneally at the occasion of decompressive punctures. The further course of the disease suggests a significant role of mistletoe in achieved symptom control, which also resulted in a considerable improvement in quality of life. The mistletoe solution was well tolerated. Relevant mechanisms of action in addition to the well-known immunomodulating properties of mistletoe could be direct cytotoxic and adjuvant effects to the concomitantly administered chemotherapy of carboplatin/paclitaxel.

Abstract Objectives: Atropine sulphate, a competitive antagonist of acetylcholine (ACh) at muscarinic receptors, was first isolated from Atropa belladonna, one of the most used and best known homeopathic medicines. It has been suggested that high potencies of homeopathic atropine sulphate might have an influence on ACh-induced contraction of smooth muscles. The aim of the study was to determine the effects of homeopathic dilutions of atropine sulphate D6, D32, and D100 compared to the potentized diluents L6, L32, and L100 on ACh-induced contraction of isolated rat ileum. Design: Forty-eight (48) ileal sections from 12 male Wistar rats were incubated in modified Krebs solutions, and the contractile activity responses to ACh obtained in the absence and presence of the test substances were recorded. Investigators and biometrician were completely blinded. Results: No significant effects of atropine sulphate D6, D32, or D100 could be found (all p > 0.4 after Bonferoni-Holm correction) compared to the potentized diluents L6, L32, and L100, respectively. These figures did not change considerably even when strict a priori criteria were applied that define a measurement as valid and comparable. Conclusions: Our experiments could not replicate previous results on the effects of homeopathic atropine.

OBJECTIVE: Lumbar spinal stenosis (LSS) is a common cause of chronic lumbar pain and disability. Conventional therapy approaches include analgesics and spinal surgery. Topical cantharidin applications are used for the treatment of severe chronic lumbar pain in traditional European medicine (TEM). We tested the pain-relieving effect of lumbar cantharidin blisters in a non-randomised controlled pilot study. PATIENTS AND METHODS: 28 consecutive patients with manifest LSS were included. The first 20 patients received a cantharidin blister, 8 patients served as controls (waiting list). Pain was assessed by means of a numeric visual analogue scale (VAS; 0 indicating no pain, 10 indicating strongest pain). Treatment started after a 3-day run-in phase, the blister was applied once for 12 h. RESULTS: Patients were comparable with respect to baseline pain. In the blister group, the pain score continuously improved from 7.2 +/- 2.1 at baseline to 2.9 +/- 2.3 (VAS) at day 7, whereas the score remained unchanged in control patients. Adjusted for baseline, the difference between the blister and the control group was estimated at 4.1 (95% CI: 2.4-5.9, p < 0.0001). The use of analgesics was slightly higher in the control group. No serious adverse events were observed. CONCLUSION: In this first study on the efficacy of cantharidin blisters, a clinically relevant pain-relieving short-term effect on LSS was observed. As the trial was non-randomised and only included a limited number of patients, the results should be interpreted with caution.

BACKGROUND: Details and effects of individualised homeopathic treatment of headache (ICD-9: 784.0) in usual care have not yet been investigated. METHODS: Prospective multi-centre observational study. Consecutive primary-care patients beginning homeopathic treatment were followed for 2 years, keeping regular records of complaint severity, health-related quality of life (QoL), and medication use. RESULTS: 230 adults (77.0% women), age 38.2 +/- 11.3 years, and 74 children (10.4 +/- 3.2 years, 55.4% girls) treated by 73 physicians were included. Patients suffered from headaches (average duration: adults 9.3 +/- 9.5 years, children 2.7 +/- 2.6 years) and other chronic diseases. Most patients (adults 90.0%, children 70.8%) had been pre-treated (usually with conventional treatment). Severity of diagnoses and complaints showed marked improvements in the first 3 months, continuing on until the end of the study. For headache, standardised effects (mean change divided by standard deviation at baseline) in adults reached 1.63 (95% CI 1.78-1.49), 2.27 (2.45-2.09), and 2.44 (2.63-2.25) at 3, 12, and 24 months, respectively. In children, the standardised effects at these time points were 1.67 (1.91-1.44), 2.55 (2.82-2.28), and 2.74 (3.03-2.46), respectively. Whilst the QoL among adults improved over time, this trend was not observed in children. Use of conventional treatment and health services decreased markedly. CONCLUSION: This observational study of patients seeking homeopathic treatment because of headache showed consistent improvements over the 24-month period. The observational and uncontrolled character of the study design does not allow conclusions on a specific relationship between treatment and the observed effects.

OBJECTIVES: One out of 4 patients visiting a general practitioner reports of a sore throat associated with pain on swallowing. This study was established to examine the immediate pain alleviating effect of a single point acupuncture treatment applied to the large intestine meridian of patients with sore throat. PATIENTS AND METHODS: Sixty patients with acute tonsillitis and pharyngitis were enrolled in this randomized placebo-controlled trial. They either received acupuncture, or sham laser acupuncture, directed to the large intestine meridian section between acupuncture points LI 8 and LI 10. The main outcome measure was the change of pain intensity on swallowing a sip of water evaluated by a visual analog scale 15 minutes after treatment. A credibility assessment regarding the respective treatment was performed. RESULTS: The pain intensity for the acupuncture group before and immediately after therapy was 5.6+/-2.8 and 3.0+/-3.0, and for the sham group 5.6+/-2.5 and 3.8+/-2.5, respectively. Despite the articulation of a more pronounced improvement among the acupuncture group, there was no significant difference between groups (Delta=0.9, confidence interval:-0.2-2.0; P=0.12; analysis of covariance). Patients' satisfaction was high in both treatment groups. The study was prematurely terminated due to a subsequent lack of suitable patients. DISCUSSION: A single acupuncture treatment applied to a selected area of the large intestine meridian was no more effective in the alleviation of pain associated with clinical sore throat than sham laser acupuncture applied to the same area. Hence, clinically relevant improvement could be achieved. Pain alleviation might partly be due to the intense palpation of the large intestine meridian. The benefit of a comprehensive acupuncture treatment protocol in this condition should be subject to further trials.

OBJECTIVES: To evaluate the details and effects of an individualized homeopathic treatment in patients with chronic low back pain in usual care. METHODS: Prospective multicenter observational study. Consecutive patients beginning homeopathic treatment in primary care practices were evaluated over 2 years by using standardized questionnaires. Diagnoses (ICD-9) and symptoms with severity, health-related quality of life (QoL), medical history, consultations, homeopathic and conventional treatments, and other health service use were recorded. RESULTS: One hundred twenty-nine adults (64.3% women, mean age 43.6 +/- 12.7 y) were treated by 48 physicians. The patients mainly had chronic low back pain (average duration 9.6 +/- 9.0 y) and other chronic diseases. Nearly all the patients (91.3%) had been pretreated. The initial case-taking took 113 +/- 36, and the case analysis took 31 +/- 38 minutes. The 7.4 +/- 8.1 subsequent consultations (duration: 23.7 +/- 15.2 min) cumulated to 204.5 +/- 184.6 minutes. The patients received an average of 6.8 +/- 6.3 homeopathic prescriptions. The severity of the diagnoses and complaints showed marked and sustained improvements with large effect sizes (Cohen's d from 1.67 to 2.55) and QoL improved accordingly (SF-36 physical component scale d = 0.33; mental component scale d = 0.54). The use of conventional treatment and health services decreased markedly: the number of patients using low back pain-related drugs was half of the baseline. DISCUSSION: Classic homeopathic treatment represents an effective treatment for low back pain and other diagnoses. It improves health-related QoL and reduces the use of other healthcare services.

BACKGROUND: Centuries ago cupping was one of the most used medical therapies worldwide but it is now regarded as an antiquated and unsafe treatment. Nevertheless it is widely used especially in Germany and China. OBJECTIVE: To investigate the effectiveness of "wet cupping" of a defined connective tissue area (over the Musculus trapezius) in patients suffering from brachialgia paresthetica nocturna. DESIGN: Monocenter, randomised, controlled, sequential clinical trial. SETTING: Section of pain management at the District Hospital of Rüdersdorf, Germany. PATIENTS: Brachialgia-patients of both sexes without age restictions were eligible if they suffered from chronical tonsillar irritations and showed pathologic indurations of the connective tissue area. INTERVENTIONS: The active group was "wet cupped" once, i.e. the skin first was scarified and then blood was drawn by applying vacuum cupping glasses. The control group was left untreated. MAIN OUTCOME MEASURE: Pre- to post-treatment change of brachialgia severeness, calculated from 1-week averages of the means of three subscales (pain, tingling and numbness), each assessed on a 0-10 numeric analogue scale. RESULTS: N=20 patients were randomised (13 women, median age 47 years). Treatment effects can be found in the active (-2.3+/-1.9 score points) but not in the control group (+0.5+/-1.0 points; p=0.002; triangle test). The results are supported by secondary outcome criteria. Adverse events were not documented in any patient. CONCLUSIONS: This study suggests short-term effects of a single wet cupping therapy, which remain at least for 1 week. As the trial lacks of an adequate and blinded placebo therapy the findings are potentially biased.

PURPOSE: The purpose of this study was to evaluate the effects of preoperative pain control education on the pain control barrier, postoperative pain and pain control satisfaction in gynecological patients. METHOD: The study was a quasi-experimental research design. There were 58 subjects who were admitted for gynecological surgery to D University Hospital in B city. Pain control education was provided individually to the experimental group one day before their operation day for 20 minutes with the 'Pain Control Guide Book' in the patient's admission room. The education book was made by researchers based on pain management references and patient interviews. For assessing the pain control barrier, a simplified version of Barriers Questionnaire was used, postoperative pain was assessed on a numeric scale(0-10) and satisfaction of pain control was assessed by one question. RESULTS: The pain control barrier(F=15.828, p<.001) and the post pain score of the experimental group was lower than that of the control group. In addition, pain control satisfaction of the experimental group(t=3.612, p<.001) was higher than the control group's. CONCLUSION: With the above results, preoperative pain control education could be an effective nursing intervention for pain control of surgical patients.

OBJECTIVES: To determine whether treatment with glucose-insulin-potassium (GIK), insulin and glucose, or insulin by itself is beneficial in limiting organ damage after acute myocardial infarction (AMI) and reducing mortality and morbidity among critically ill hyperglycaemic patients. METHODS: Systematic review of randomized controlled trials. MAIN OUTCOME MEASURE: To assess whether tight glycaemic control reduces morbidity and mortality. STUDIES REVIEWED: Randomized controlled trials of insulin-based regimens in the treatment of critically ill patients. RESULTS: Nine hundred and twenty-four potentially relevant studies were identified and screened for retrieval. Of these, 16 randomized controlled trials met the inclusion criteria (Table 1). Ten studies examined the effects of GIK, and six of these studies reported a mortality reduction with GIK treatment in addition to enhanced myocardial performance. Five studies examined the administration of insulin. Among these studies, tight glycaemic control of blood glucose in one study was shown to reduce morbidity and mortality of patients in intensive care. Only one study examined insulin/glucose therapy, and it showed a post-myocardial infarction mortality reduction of one year. 1Description of Studies in Order of Treatment(Glucose-Insulin-Potassium-GIK)Study No.SourceYearStudy titleStudy design/descriptionStudy findings-whether tight glycaemic control improves morbidity and mortality2Lazar et al.1997GIK solutions enhance recovery after urgent coronary artery bypass graftingStudy undertaken to determine whether GIK solutions would benefit patients undergoing coronary artery bypass grafting.Although no mortality was evident in either group. GIK therapy enhances myocardial performance and results in faster recovery from urgent coronary artery bypass grafting.The study group consisted of 30 patients with unstableangina who required coronary artery bypass surgery: 15 patients randomized to treatment with GIK solution administered intravenously after induction of anaesthesia and continued for 12 h after aortic unclamping, the remaining 15 patients received intravenous 5% dextrose in water.3Diaz et al.1998Metabolic modulation of AMI: The ECLA GIK pilot trialStudy conducted to evaluate the impact of a GIK infusion administered during the first few hours of AMI.A trend toward a non-significant reduction in major and minor in-hospital events was observed in patients allocated to GIK. However, in the patients treated with reperfusion strategies, a statistically significant reduction in mortality and a consistent trend toward fewer in-hospital events in the GIK group was observed.A total of 407 patients with suspected AMI were studied. In a ratio of 2 : 1 patients, 268 were randomized to receive GIK (high or low dose) and 139 to receive control.4Scott et al.1999GIK infusions in the treatment of acute stroke patients with mild to moderate hyperglycaemia. The glucose-insulin in stroke trial (GIST)Study designed to determine whether glucose/insulin induced and maintained euglycaemia in acute stroke patients with mild to moderate hyperglycaemia can improve outcome after stroke. Fiftythree acute stroke patients with mild to moderate hyperglycaemia (7-17 mmol/L) were studied: 25 randomized to treatment with a GIK infusion (insulin concentration in the GIK was altered according to BM glucose values) and 28 to the control, which were administered as sodium chloride infusion.Results confirm that GKI infusion in mild to moderate hyperglycaemia following acute stroke is a safe, practical, and pragmatic intervention that effectively lowers the plasma glucose levels to within normal range; however, the beneficial effects of this treatment remain to be elucidated.5Ceremuzynski et al.1999Low-dose GIK is ineffective in AMI: results of a randomized multi-centre Pol-GIK trialStudy designed to assess the clinical efficacy of GIK infusion in AMI.Low-dose GIK treatment does not improve the survival and clinical course in AMI.The study consisted of 954 patients: 494 randomized to treatment with low-dose GIK infusion and 460 to the control group, which was administered sodium chloride by IV infusion.Total mortality at 35 days was significantly higher in the GIK infusion group than in the control group.6Besogul et al.1999Chemical, biochemical and histochemical assessment of pre-treatment with GIK for patients undergoing mitral valve replacement in the third and forth functional groups of the New York Heart Association.A study designed to investigate the potentially beneficial effects of pre-operative treatment with GIK for patients undergoing mitral valve replacement.No significant reduction in mortality was evident throughout the period of the trial; however, the patients receiving GIK required less inotropic support, had fewer ventricular arrhythmias, and exhibited improved haemodynamic indices: cardiac output increased & systemic vascular resistance decreased.A total of 30 patients were studied: 15 randomly assigned to treatment with GIK infusion and 15 to the control group, which was administered an equivalent volume of sodium chloride.7Lazar et al.2000GIK solutions improve outcomes in diabetic patients who have coronary artery operations.Study undertaken to determine whether GIK would improve myocardial performance and limit morbidity after coronary artery bypass grafting in diabetic patients.Although no mortality was evident in either group. GIK therapy enhances myocardial performance and results in faster recovery from urgent coronary artery bypass grafting.A total of 40 patients were studied: 20 randomized to receive a GIK infusion and 20 to the control group, which received 5% dextrose in water.9Ulgen et al.2001The effect of GIK solution on ventricular late potentials and heart rate variability in AMI.Study designed to investigate the effects of GIK solution on ventricular late potentials (VLP) and high rate variability (HRV) during the early period of AMI.Although treatment with GIK solution did not find a statistically significant reduction in mortality, the results suggest that GIK therapy in the early periods of AMI shows beneficial effects: decreased post-myocardial infarction angina and ischaemia.(High rate variability and presence of VLP are known to correlate with an increased risk of ventricular tachycardia and sudden death in AMI.)A total of 72 patients were studied: 34 randomized to treatment with GIK and 38 to the placebo.10Szabo et al.2001Effects of high-dose GIK on myocardial metabolism after coronary surgery in patients with type 2 diabetes.Study designed to investigate the effects of high-dose GIK on myocardial substrate utilization after coronary surgery in patients with type 2 diabetes.Although no mortality was evident in either group, it can be concluded that high-dose GIK significantly enhances myocardial performance.A total of 20 patients were randomly allocated: 10 received high-dose GIK infusion post-operatively and the remaining 10 in the control group received standard post-operative care, including insulin infusion if required, to maintain blood glucose below 10 mmol/L.11Smith et al.2002Coronary revascularisation: a procedure in transition from on-pump to off-pump? The role of GIK revisited in a randomized, placebo-controlled studyA study designed to investigate an optimized GIK solution regimen as an alternative myocardial protective strategy in off-pump coronary artery bypass graft surgery and as a supplement to conventional coronary artery bypass surgery using cardiopulmonary bypass (CPB). The study consisted of 44 patients scheduled for elective multi vessel surgery using either conventional CPB (n = 22) or off-pump coronary artery bypass techniques (n = 22). Pre-ischaemic, ischaemic, and post-ischaemic administration of GIK solution was carried out,(optimally dosed to ensure non-esterfied fatty acid suppression (NEFA), and supplemented with magnesium (a glycolytic cofactor).GIK solution did not achieve any clinical benefit. However, compared with CPB, off-pump coronary artery bypass surgery significantly reduced ischaemic injury and post-operative infections.13Lell et al.2002GIK infusion for myocardial protection during off-pump coronary artery surgery.Study undertaken to evaluate the clinical effectiveness of GIK infusion in preventing myocardial damage and maintaining cardiac performance in patients undergoing off-pump myocardial revascularization.A GIK infusion used as an adjunct to reperfusion therapy for AMI causes insulin-resistant hyperglycaemia in elective off-pump coronary artery bypass patients, with no demonstrable benefit.A total of 46 patients undergoing off-pump coronary artery bypass were studied: 21 were randomly assigned to treatment with GIK infusion and 20 to the control group, which was administered sodium chloride (five patients were excluded due to cardiovascular instability).Insulin-only Infusion16Ingels et al.2006Strict blood glucose control with insulin during intensive care after cardiac surgery: impact on 4 years survival, dependency on medical care, and quality of lifeSub-analysis and follow-up study of a large, randomized controlled trial on the effects of intensive insulin therapy during critical illnessShort-term survival benefit was obtained after 4 years, without inducing increased medical care requirements, with insulin-titrated glycaemic control maintained during intensive care after cardiac surgery.15Van den Berghe et al.2006Intensive insulin therapy in the medical ICUA prospective, randomized, controlled study of adult patients admitted to our medical ICU. On admission, patients were randomly assigned to strict normalization of blood glucose levels (80-110 mg/dL, 4.4-6.1 mmol/L) with the use of insulin infusion or to conventional therapy (insulin administered when the blood glucose level exceeded 215 mg per/dL (12 mmol/L), with the infusion tapered when the level fell below 180 mg/dL (10 mmol/L)). There was a history of diabetes in 16.9% of the patients.Intensive insulin therapy significantly reduced morbidity, but not mortality, among all patients in the medical ICU. Although the risk of subsequent death and disease was reduced in patients treated for three or more days, these patients could not be identified before therapy.8Van den Berghe et al.2001Intensive insulin therapy in critically ill patientsStudy designed to assess whether normalization of blood glucose levels with intensive insulin therapy reduces mortality and morbidity among critically ill patients.Intensive insulin therapy to maintain blood glucose at or below 6.1 mmol/L reduces morbidity and mortality among critically ill patients in the surgical ICU.A total of 1548 were studied: 783 randomly assigned to the intensive treatment group with the aim of maintaining normoglycaemia (4.4-6.1 mmol/L) and 765 to the conventional group in which an insulin infusion was titrated to maintain blood glucose levels between 10 & 11.1 mmol/L.12Groban et al.2002Intra-operative insulin therapy does not reduce the need for inotropic or anti-arrhythmic therapy after cardiopulmonary bypassStudy designed to determine whether attempted glucose control through intra-operative insulin therapy reduces the need for inotropic or anti-arrhythmic therapy after cardiopulmonary bypass.Intra-operative insulin therapy did not reduce mortality or the use of inotropic or anti-arrhythmic support after cardiac surgery with CPB.A total of 381 patients were studied: 188 randomized to treatment with insulin infusion in an attempt to maintain blood glucose within set parameters and 193 to the control group, which was administered sodium chloride.14Rao et al.2002The insulin cardioplegia trial: myocardial protection for urgent coronary artery bypass graftingStudy undertaken to evaluate the clinical impact of insulin-enhanced cardioplegia on patients at high risk and undergoing coronary artery bypass surgery for unstable angina.Despite encouraging results from smaller studies, the trial failed to demonstrate any clinical benefit of insulin-enhanced cardioplegia solution for patients undergoing high-risk isolated coronary artery bypass grafting.A total of 1127 patients were studied: 557 were randomly assigned at operation to receive cardioplegic solution supplemented with insulin and 570 were assigned to a placebo.Insulin-Glucose Method of Administration1Malmberg et al.1995Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with AMI : effects on mortality at one year.Study investigating how insulin-glucose infusion followed by multi-dose insulin treatment in diabetic patients with AMI affected mortality during the subsequent 12 months of follow-up.Insulin-glucose infusion followed by multi-dose insulin regime statistically improved long-term prognosis in diabetic patients with AMI.A total of 620 patients were studied: 306 were randomized to treatment with insulin-glucose infusion followed by multi-dose subcutaneous insulin for more that 3 months, and 314 to conventional therapy (insulin administered only if deemed clinically necessary). CONCLUSIONS: There is increasing evidence that maintaining normoglycaemia and treatment with insulin-based regimens is beneficial in limiting organ damage and significantly reduces both morbidity and mortality in critically ill patients who require intensive care therapy. Copyright (c) 2007 John Wiley & Sons, Ltd.

OBJECTIVES: To evaluate the clinical effectiveness, safety, tolerability and cost-effectiveness of etanercept and efalizumab for the treatment of moderate to severe chronic plaque psoriasis. DATA SOURCES: Major electronic databases and several Internet resources were searched up to April 2004. REVIEW METHODS: Systematic reviews were undertaken of the efficacy, safety and economic reviews of etanercept and efalizumab. An existing systematic review of the efficacy and safety of other treatments was also updated. Economic models supplied by the manufacturers of etanercept and efalizumab were critiqued. An economic model was then developed of etanercept and efalizumab in the treatment of moderate to severe chronic plaque psoriasis. RESULTS: The review of the clinical evidence identified a total of 39 published and three unpublished studies: eight randomised controlled trials (RCTs) of the efficacy of etanercept (three trials) and efalizumab (five); 10 studies of the adverse effects of the interventions; and 24 RCTs of the efficacy of the other treatments for moderate to severe psoriasis. The trials of the efficacy of the interventions were all double-blind and placebo-controlled trials and generally of good quality, but three of the five efalizumab trials were poorly reported. A total of 1347 patients were included in the etanercept trials and 2963 in the efalizumab trials. Data on the efficacy of etanercept 25 mg twice a week for 12 weeks were available from three RCTs. On average, active treatment resulted in 62% of patients achieving a Psoriasis Area and Severity Index (PASI) 50, 33% achieving a PASI 75, 11% achieving a PASI 90 and 40% were assessed as clear or almost clear. These figures are not adjusted for changes relative to placebo. Improvement in quality of life as assessed by mean percentage change in Dermatology Life Quality Index (DLQI) was around 59% with etanercept 25 mg twice a week compared with 9% with placebo, and all mean differences that could be calculated were statistically significantly in favour of etanercept. Data on the efficacy of etanercept 50 mg twice a week for 12 weeks were available from two RCTs. Across the two trials, the proportion of patients achieving PASI 50, 75 and 90 was 76, 49 and 21%, respectively; the pooled relative risks were all statistically significantly in favour of etanercept. The findings for mean PASI after treatment, mean percentage change in PASI from baseline and mean percentage change in DLQI also demonstrated the efficacy of etanercept treatment. Evidence from one RCT indicates that the response to etanercept is maintained post-treatment, at least in the medium term, and data from uncontrolled follow-up phases reflect and extend these findings. Efalizumab at a dose of 1 mg/kg once a week subcutaneously was studied in five RCTs. Across these trials, 12 weeks of active treatment resulted in an average of 55% of patients achieving PASI 50, 27% PASI 75, 4.3% PASI 90 and 27% clear or minimal psoriasis status. These figures are not adjusted for changes relative to placebo. There is no evidence from RCTs that the response to efalizumab 1 mg/kg once a week is maintained when treatment continues beyond 12 weeks, and long-term follow-up data relate to a range of doses and are poorly reported and so cannot be used to draw even tentative conclusions regarding the long-term efficacy of efalizumab. Uncontrolled data from trial follow-up suggest that time to relapse may be around 60 days. No data indicating the existence or absence of any rebound in psoriasis after discontinuation of efalizumab were identified. There is no evidence relating to the efficacy of efalizumab upon retreatment. A mixed treatment comparison analysis found a higher response rate in terms of PASI 50, 75 and 90 with etanercept than with efalizumab. Injection site reactions appear to be the most common adverse effects of etanercept. Overall, etanercept appears to be well tolerated in short- and long-term use, although many of the long-term data are not from patients with psoriasis. Headache, chills and, to a lesser extent, nausea, myalgia, pain and fever are the common adverse events associated with efalizumab. Overall, withdrawal rates due to adverse events are low. Longer term data for efalizumab are not readily available for evaluation, but the adverse events data up to 3 years appear to reflect those over 12 weeks and to remain stable. Unfortunately, few data for serious infections and serious adverse events with efalizumab are available. For the primary analysis comparing etanercept, efalizumab and supportive care, the results of the York Model suggest that the biological therapies would only be cost-effective for all patients with moderate to severe psoriasis if the NHS were willing to pay over pound60,000 per QALY gained. In patients with poor baseline quality of life (fourth quartile DLQI), efalizumab, etanercept 25 mg (intermittent), etanercept 25 mg (continuous) and etanercept 50 mg (intermittent) would be cost-effective as part of a treatment sequence if the NHS were willing to pay pound45,000, pound35,000, pound45,000 and pound65,000 per QALY gained, respectively. In patients who are also at high risk of inpatient hospitalisation (21 days per annum), these therapies would be cost-effective as part of a sequence as long as the NHS were willingness to pay pound25,000, pound20,000, pound25,000 and pound45,000 per QALY gained, respectively. As part of a secondary analysis including a wider range of systemic therapies as comparators, the York Model found that it would only be cost-effective to use etanercept and efalizumab in a sequence after methotrexate, ciclosporin and Fumaderm. CONCLUSIONS: Clinical trial data indicate that both etanercept and efalizumab are efficacious in patients who are eligible for systemic therapy, but the economic evaluation demonstrates that these biological therapies are likely to be cost-effective only in patients with poor baseline QoL and who are at risk of hospitalisation. Efficacy trials conducted in the specific population for which etanercept and efalizumab are licensed are required, as are long-term comparisons of etanercept and efalizumab with other treatments for moderate to severe psoriasis. Long-term efficacy trials and safety/tolerability data for patients treated with etanercept or efalizumab are required, as are trials on the response of specific subtypes of psoriasis to different drugs. Research on the rate of inpatient hospitalisation in patients with moderate to severe psoriasis is warranted, and the effect of treatment on this rate.

Articular cartilage has poor reparative capacities, and once damaged cartilage lesions remain chronic and can lead to osteoarthritis. Over the last decade, several innovative therapies have been introduced to promote the regeneration of articular cartilage while sustaining sufficient mechanical stress and permitting a pain free motion. An important measure of outcome is the morphological characterization of the repair tissue in order to allow for cross-study evaluation. The International Cartilage Repair Society has developed a analogue visual scale to quantify repair tissue, which is described in this paper.

BACKGROUND: Proponents of early intervention have argued that outcome might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection and phase-specific treatment. Both elements may be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia, but it is unclear how far early detection, phase-specific treatments, and the use of early intervention teams are underpinned by evidence of effectiveness. OBJECTIVES: To evaluate the effects of:(a) early detection;(b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first episode psychosis. SEARCH STRATEGY: We searched CINAHL (1982-2002), The Cochrane Controlled Trials Register (November 2001), The Cochrane Schizophrenia Group Register (July 2003), EMBASE (1980-2002), MEDLINE (1966-2002), PsycINFO (1967-2002), reference lists and contacted the European First Episode Network (2003). For the 2006 update we searched the Cochrane Schizophrenia Group's register. SELECTION CRITERIA: We included all randomised controlled trials designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first episode psychosis. Eligible interventions, alone and in combination, included early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. DATA COLLECTION AND ANALYSIS: We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). MAIN RESULTS: We included seven studies with a total of 941 participants. Six studies were small with numbers of participants ranging between 56 and 83, and one study randomised 547 people. None of the studies had similar interventions and therefore they were analysed separately. One small Australian trial (n=59) was concerned with a phase-specific intervention (low dose risperidone and cognitive behavioural therapy) for people with prodromal symptoms. This group were significantly less likely to develop psychosis at a six month follow up than people who only received care from a specialised team which did not involve phase-specific treatment (n=59, RR 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20). This effect was not significant at 12 month follow up (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). A UK-based study (EDIE) randomised 60 people with prodromal symptoms, to cognitive behavioural therapy (CBT) or a monitoring group. Only two outcomes were reported: leaving the study early and transition to psychosis, both sets of data were non-significant. A Chinese trial used a phase-specific intervention (family therapy) plus out patient care trial for people in their first episode of psychosis and found reduced admission rates care compared with those who received only outpatient care (n=83, RR 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The applicability of this finding was, however, questionable. One Dutch study (n=76) comparing phase-specific intervention (family therapy) plus specialised team with specialised team for people in their first episode of schizophrenia found no difference between intervention and control groups at 12 months for the outcome of relapse (n=76, RR 1.05 CI 0.4 to 3.0). The large Scandinavian study (n=547) allocated people with first episode schizophrenia to integrated treatment (assertive community treatment plus family therapy, social skills training and a modified medication regime) or standard care. Global state outcome GAF significantly favoured integrated treatment (n=419, WMD -3.71 CI -6.7 to -0.7) by one year, but by two years data were non-significant. Rates of attrition were significantly lower (n=547, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) for integrated treatment by one and two year follow-up. PRIME (USA) was the only double blind study and allocated people with prodromal symptoms to olanzapine or placebo. No significant differences were found between olanzapine and placebo in preventing conversion to psychosis by about 12 months (n=60, RR 0.58 CI 0.3 to 1.2). Clinical Global Impression change scores 'severity of illness' were equivocal by 12 months. Scale of Prodromal Symptoms (SOPS) scores were also equivocal and the PANSS, total, positive and negative outcomes were non-significant. There were no significant differences between the olanzapine and placebo group on adverse effects rating scales - SAS, BAS and AIMS scores; Weight gain was significantly higher in the olanzapine group (n=59, WMD 7.63 CI 4.0 to 11.2) by 12 months. Finally one more Australian study included people in their first episode of psychosis who were acutely suicidal and allocated people to phase-specific cognitively orientated therapy or standard care. Outcome data for leaving the study early and suicide were equivocal. AUTHORS' CONCLUSIONS: We identified insufficient trials to draw any definitive conclusions. The substantial international interest in early intervention offers an opportunity to make major positive changes in psychiatric practice, but making the most of this opportunity requires a concerted international programme of research to address key unanswered questions.