8          References

8.1       List of Literature

AWMF Directions of the German Interdisciplinary Association for Pain therapy : Treatment of acute perioperative and posttraumatic pain

Abstract         The studies included in this meta-analysis predominantly investigated the effects of TENS in thoracic and abdominal surgical procedures. Only one study investigated the effect of TENS in meniscus surgery; here the individual result showed a positive effect. Reduced need for analgesics by applying TENS after surgery in the urogenital area was observed in two randomized studies. 21 randomized studies could establish a significant positive impact of TENS on the post-operative use of analgesics

Bjordal, Jan Magnus; Johnson, Mark I.; Ljunggreen, Anne Elisabeth (2003): Transcutaneous electrical nerve stimulation (TENS) can reduce postoperative analgesic consumption. A meta-analysis with assessment of optimal treatment parameters for postoperative pain. In: European journal of pain, Jg. 7, H. 2, S. 181–188.

Abstract   AIM: We investigated the literature of randomised placebo-controlled trials to find out if transcutaneous electrical nerve stimulation (TENS) or acupuncture-like transcutaneous electrical nerve stimulation (ALTENS) can reduce analgesic consumption after surgery. RESULTS: Subgroup analysis for adequate treatment (pulse frequency: 1-8Hz [ALTENS] or 25-150Hz [TENS], current intensity: “strong, definite, subnoxious, maximal tolerable” or above 15mA, and electrode placement in the incision area) were performed. Twenty-one randomised, placebo-controlled trials with a total of 1350 patients were identified. For all trials, the mean reduction in analgesic consumption after TENS/ALTENS was 26.5% (range -6 to +51%) better than placebo. Eleven of the trials compromising 964 patients, had reports which stated that a strong, subnoxious electrical stimulation with adequate frequency was administered. They reported a mean weighted reduction in analgesic consumption of 35.5% (range 14-51%) better than placebo. In nine trials without explicit confirmation of sufficient current intensity and adequate frequency, the mean weighted analgesic consumption was 4.1% (range -10 to +29%) in favour of active treatment. The difference in analgesic consumption was significantly (p=0.0002) in favour of adequate stimulation. The median frequencies used in trials with optimal treatment was 85Hz for TENS and 2Hz in the only trial that investigated ALTENS. CONCLUSION: TENS, administered with a strong, subnoxious intensity at an adequate frequency in the wound area, can significantly reduce analgesic consumption for postoperative pain.

Bracken, Michael B. (2005): Genomic epidemiology of complex disease: the need for an electronic evidence-based approach to research synthesis. In: American journal of epidemiology, Jg. 162, H. 4, S. 297–301.

Abstract   Modern microarray genotyping now permits simultaneous analysis of tens of thousands of polymorphisms, and this technology is being widely used to associate the role of genes with the etiology of complex disease. Genome-wide hypothesis-free mapping will also increasingly generate candidate genes that require further testing in association studies. At the same time, genetic effects are increasingly observed to be buffered by a wide array of biologic mechanisms that evolved to protect the genome from environmental insult and that serve to obscure observation of direct effects of polymorphisms on a disease phenotype. These two forces combine to make replication of genomic epidemiology extraordinarily difficult. Traditional research synthesis of emerging bodies of genomic epidemiology is problematic and often quickly outdated. The author proposes that electronic evidence-based methodology, perhaps modeled after that used by the Cochrane Collaboration in clinical medicine, would facilitate the systematic preparation and frequent updating of systematic reviews, which is essential for identifying valid and replicable gene-disease associations.

Brosseau, Lucie; Milne, Sarah; Robinson, Vivian; Marchand, Serge; Shea, Beverley; Wells, George; Tugwell, Peter (2002): Efficacy of the transcutaneous electrical nerve stimulation for the treatment of chronic low back pain: a meta-analysis. In: Spine, Jg. 27, H. 6, S. 596–603.

Abstract   BACKGROUND: Low back pain affects a large proportion of the population. Transcutaneous electrical nerve stimulation (TENS) was introduced more than 30 years ago as an alternative therapy to pharmacologic treatments for chronic pain. However, despite its widespread use, the efficacy of TENS is still controversial. PURPOSE: The aim of this meta-analysis was to determine the efficacy of TENS in the treatment of chronic low back pain. METHODS: The authors searched MEDLINE, EMBASE, PEDro, and the Cochrane Controlled Trials Register up to June 1, 2000. Only randomized controlled clinical trials of TENS for the treatment of patients with a clinical diagnosis of chronic low back pain were included. Abstracts were excluded unless further data could be obtained from the authors. Two reviewers independently selected trials and extracted data using predetermined forms. DATA ANALYSIS: Heterogeneity was tested with Cochrane’s Q test. A fixed effects model was used throughout for continuous variables, except where heterogeneity existed, in which case, a random effects model was used. Results are presented as weighted mean differences with 95% confidence intervals, where the difference between the treated and control groups was weighted by the inverse of the variance.
Standardized mean differences were calculated by dividing the difference between the treated and control by the baseline variance. Standardized mean differences were used when different scales were integrated to measure the same concept. Dichotomous outcomes were analyzed with odds ratios. MAIN RESULTS: Five trials were included, with 170 subjects randomized to the placebo group receiving sham TENS and 251 subjects receiving active TENS (153 for conventional mode, 98 for acupuncture-like TENS). The schedule of treatments varied greatly between studies ranging from one treatment/day for 2 consecutive days, to three treatments/day for 4 weeks. There were no statistically significant differences between the active TENS group compared with the placebo TENS group for any outcome measures. Subgroup analysis performed on TENS application and methodologic quality did not demonstrate a significant statistical difference (P > 0.05). Remaining preplanned subgroup analysis was not conducted because of the small number of included trials and the variety of outcome measures reported. CONCLUSION: The results of the meta-analysis present no evidence to support the use or nonuse of TENS alone in the treatment of chronic low back pain. Considering the small number of studies responding to the criteria to be included in this meta-analysis, it is clear that more appropriately designed studies are needed before a final conclusion. Clinicians and researchers should consistently report the characteristics of the TENS device and the application techniques used. New trials on TENS should make use of standardized outcome measures. This meta-analysis lacked data on how TENS efficacy is affected by four important factors: type of applications, site of application, treatment duration of TENS, and optimal frequencies and intensities.

Cameron, M.; Lonergan, E.; Lee, H. (2003): Transcutaneous electrical nerve stimulation (TENS) for dementia. In: Cochrane database of systematic reviews, H. 3.

Abstract   BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is the application of an electrical current through electrodes attached to the skin. The commonest clinical application of TENS is pain control. TENS is also used occasionally for the treatment of a range of neurological and psychiatric conditions including drug and alcohol dependence, headaches, and depression. TENS is rarely used for the treatment of dementia. However, since the early 1990s a number of studies carried out by a group in the Netherlands, and one study carried out by a group in Japan, suggest that TENS applied to the back or head may improve cognition and behaviour in patients with Alzheimer’s disease or multi-infarct dementia. It was claimed that applying TENS could benefit patients with dementia by altering the activity of various neurotransmitters, or by increasing brain activity and thereby retarding neural degeneration and stimulating regenerative processes. It is claimed that application of TENS to the head may also alleviate the sleep disorders associated with dementia. OBJECTIVES: The aim of this review is to determine the effectiveness and safety of transcutaneous electrical nerve stimulation (TENS) in the treatment of dementia. Secondary objectives of this review are to determine whether any effect of treatment of dementia with TENS is influenced by any treatment parameters or patient features, including: the duration of treatment, electrical waveform, current amplitude, pulse duration and frequency and the patient’s type or severity of cognitive impairment. SEARCH STRATEGY: The trials were identified from a search of the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 10 December 2002 using the terms TENS, transcutaneous, “transcutaneous electrical nerve stimulation”, and “electric stimulation”. The CDCIG Specialized Register contains records from all major health care databases and many ongoing trials databases and is regularly updated. SELECTION CRITERIA: All RCTs in which TENS was used as an intervention for people with dementia were included in this review. This included peripherally applied transcutaneous electrical stimulation as well as transcutaneous electrical stimulation applied to the head (also known as cranial electrical stimulation (CES)). DATA COLLECTION AND ANALYSIS: All RCTs that fulfilled the inclusion criteria for the review and for which sufficient data were available were included in this meta-analysis. Two reviewers extracted the data from the included trials. All except one of the included trials used similar outcome measures. Data of the same outcome measures were combined for analysis. MAIN RESULTS: Eight trials were included in the review but only 3 trials could be included in the meta-analysis. Sufficient data to include the other trials in the meta-analysis could not be obtained. From this limited analysis it appears that TENS produced a statistically significant improvement directly after treatment in: delayed recall of 8 words in one trial, face recognition in two trials and motivation in one trial however, no effect of TENS was found on any of the many other neuropsychological and behavioural measures evaluated either directly after TENS treatment or 6 weeks after treatment was completed. REVIEWER’S CONCLUSIONS: Although a number of studies suggest that TENS may produce short lived improvements in some neuropsychological or behavioural aspects of dementia, the limited presentation and availability of data from these studies does not allow definite conclusions on the possible benefits of this intervention. Since most of the currently published studies are well designed, although the numbers of subjects in each study is small, analysis of the complete original data from these and/or future studies may allow more definitive conclusions to be drawn.

Ernst, E.; Pittler, M. H. (1998): The effectiveness of acupuncture in treating acute dental pain: a systematic review. In: British dental journal, Jg. 184, H. 9, S. 443–447.

Abstract   OBJECTIVE: Acupuncture is frequently advocated as an effective treatment of dental pain. The question whether or not it is effective for this indication remains controversial. The aim of this systematic review therefore was to assess the effectiveness of acupuncture in dental pain. DATA SOURCES: Four electronic databases were searched: Medline, Embase, CISCOM, and the Cochrane Library. Only controlled trials were included in this review. DATA EXTRACTION: Information was extracted from included studies and entered on standard forms independently by both authors. Methodological quality was assessed using the Jadad score. MAIN RESULTS: 16 such studies were located. The majority of these trials imply that acupuncture is effective in dental analgesia. However, important questions remain unanswered. CONCLUSION: It is concluded that acupuncture can alleviate dental pain and that future investigations should define the optimal acupuncture technique and its relative efficacy compared with conventional methods of analgesia.

Ezzo, J. M.; Richardson, M. A.; Vickers, A.; Allen, C.; Dibble, S. L.; Issell, B. F. et al. (2006): Acupuncture-point stimulation for chemotherapy-induced nausea or vomiting. In: Cochrane database of systematic reviews, H. 2.

Abstract   BACKGROUND: There have been recent advances in chemotherapy-induced nausea and vomiting using 5-HT(3) inhibitors and dexamethasone. However, many still experience these symptoms, and expert panels encourage additional methods to reduce these symptoms. OBJECTIVES: The objective was to assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. SEARCH STRATEGY: We searched MEDLINE, EMBASE, PsycLIT, MANTIS, Science Citation Index, CCTR (Cochrane Controlled Trials Registry), Cochrane Complementary Medicine Field Trials Register, Cochrane Pain, Palliative Care and Supportive Care Specialized Register, Cochrane Cancer Specialized Register, and conference abstracts. SELECTION CRITERIA: Randomized trials of acupuncture-point stimulation by any method (needles, electrical stimulation, magnets, or acupressure) and assessing chemotherapy-induced nausea or vomiting, or both. DATA COLLECTION AND ANALYSIS: Data were provided by investigators of the original trials and pooled using a fixed effect model. Relative risks were calculated on dichotomous data. Standardized mean differences were calculated for nausea severity. Weighted mean differences were calculated for number of emetic episodes. MAIN RESULTS: Eleven trials (N = 1247) were pooled. Overall, acupuncture-point stimulation of all methods combined reduced the incidence of acute vomiting (RR = 0.82; 95% confidence interval 0.69 to 0.99; P = 0.04), but not acute or delayed nausea severity compared to control. By modality, stimulation with needles reduced proportion of acute vomiting (RR = 0.74; 95% confidence interval 0.58 to 0.94; P = 0.01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% confidence interval 0.60 to 0.97; P = 0.02), but manual acupuncture did not; delayed symptoms for acupuncture were not reported. Acupressure reduced mean acute nausea severity (SMD = -0.19; 95% confidence interval -0.37 to 0.01; P = 0.04) but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. AUTHORS’ CONCLUSIONS: This review complements data on post-operative nausea and vomiting suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies combining electroacupuncture with state-of-the-art antiemetics and in patients with refractory symptoms are needed to determine clinical relevance. Self-administered acupressure appears to have a protective effect for acute nausea and can readily be taught to patients though studies did not involve placebo control. Noninvasive electrostimulation appears unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Hay, E. M.; Dziedzic, K.; Sim, J. (1999): Treatment options for regional musculoskeletal pain: what is the evidence. In: Baillière’s best practice & research. Clinical rheumatology, Jg. 13, H. 2, S. 243–259.

Abstract   Decisions about the best treatment options for patients with regional musculoskeletal pain must be made despite a lack of clear diagnostic criteria, an absence of robust outcome measures by which to assess response, and a paucity of evidence from high-quality randomized controlled trials. Although the randomized controlled trial is considered to be the ‘gold standard’ research design, it does not lend itself easily to the evaluation of all management strategies. This chapter explores these issues from a research perspective and reviews the various types of evidence available to help practitioners make informed decisions. The current evidence from systematic reviews in this area is summarized in the final part of the chapter.

Johnson, Michael; Martinson, Melissa (2007): Efficacy of electrical nerve stimulation for chronic musculoskeletal pain: a meta-analysis of randomized controlled trials. In: Pain, Jg. 130, H. 1-2, S. 157–165.

Abstract         Johnson and Martinson (2007) were able to show that pain can be significantly reduced by applying transcutaneous electrical nerve stimulation. TENS application is significantly superior to placebo treatment. Johnson and Martinson also showed that the consumption of pain medicine, as well as the necessity for additional pain treatment, was reduced.

Khadilkar, Amole; Odebiyi, Daniel Oluwafemi; Brosseau, Lucie; Wells, George A. (2008): Transcutaneous electrical nerve stimulation (TENS) versus placebo for chronic low-back pain. In: Cochrane database of systematic reviews, H. 4.

Abstract   BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) was introduced more than 30 years ago as a therapeutic adjunct to the pharmacological management of pain. However, despite widespread use, its effectiveness in chronic low-back pain (LBP) is still controversial. OBJECTIVES: To determine whether TENS is more effective than placebo for the management of chronic LBP. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PEDro and CINAHL were searched up to July 19, 2007. SELECTION CRITERIA: Only randomized controlled clinical trials (RCTs) comparing TENS to placebo in patients with chronic LBP were included. DATA COLLECTION AND ANALYSIS: Two review authors independently selected the trials, assessed their methodological quality and extracted relevant data. If quantitative metaanalysis was not possible, a qualitative synthesis was performed, taking into consideration 5 levels of evidence as recommended by the Cochrane Collaboration Back Review Group. MAIN RESULTS: Four high-quality RCTs (585 patients) met the selection criteria. Clinical heterogeneity prevented the use of meta-analysis. Therefore, a qualitative synthesis was completed. There was conflicting evidence about whether TENS was beneficial in reducing back pain intensity and consistent evidence in two trials (410 patients) that it did not improve back-specific functional status. There was moderate evidence that work status and the use of medical services did not change with treatment. Conflicting results were obtained from two studies regarding generic health status, with one study showing no improvement on the modified Sickness Impact Profile and another study showing significant improvements on several, but not all subsections of the SF-36 questionnaire. Multiple physical outcome measures lacked statistically significant improvement relative to placebo. In general, patients treated with acupuncture-like TENS responded similarly to those treated with conventional TENS. However, in two of the trials, an inadequate stimulation intensity was used for acupuncture-like TENS, given that muscle twitching was not induced. Optimal treatment schedules could not be reliably determined based on the available data. Adverse effects included minor skin irritation at the site of electrode placement. AUTHORS’ CONCLUSIONS: At this time, the evidence from the small number of placebo-controlled trials does not support the use of TENS in the routine management of chronic LBP. Further research is encouraged.

Kirpalani, Dhiruj; Mitra, Raj (2008): Cervical facet joint dysfunction: a review. In: Archives of physical medicine and rehabilitation, Jg. 89, H. 4, S. 770–774.

Abstract   OBJECTIVE: To review the relevant literature on cervical facet joint dysfunction and determine findings regarding its anatomy, etiology, prevalence, clinical features, diagnosis, and treatment. DATA SOURCES: A computer-aided search of several databases was performed, including Medline (1966 to present), Ovid (1966 to present), and the Cochrane database (1993 to present). STUDY SELECTION: Selected articles had the following criteria: (1) all articles analyzed cervical facet joint pain-anatomy, prevalence, etiology, diagnosis, treatment; (2) only full, published articles were studied, not abstracts; and (3) all articles were published in English. DATA EXTRACTION: All articles were critically evaluated and included the following categories: randomized controlled trials, meta-analyses, uncontrolled clinical trials, uncontrolled comparison studies, nonquantitative systematic reviews, and literature-based reviews. DATA SYNTHESIS: We examined 45 references that consisted of 44 journal articles and relevant sections from 1 textbook. Cervical facet joints have been well established in the literature as a common nociceptive pain generator, with an estimated prevalence that ranges from 25% to 66% of chronic axial neck pain. No studies have reported clinical examination findings that are diagnostic for cervical facet mediated pain. CONCLUSIONS: Overall the literature provides very limited information regarding the treatment of this condition, with only radiofrequency neurotomy showing evidence of effectively reducing pain from cervical facet joint dysfunction.

Lee, A.; Done, M. L. (1999): The use of nonpharmacologic techniques to prevent postoperative nausea and vomiting: a meta-analysis. In: Anesthesia and analgesia, Jg. 88, H. 6, S. 1362–1369.

Abstract   We assessed the efficacy of nonpharmacologic techniques to prevent postoperative nausea and vomiting (PONV) by systematic review. These studies included acupuncture, electroacupuncture, transcutaneous electrical nerve stimulation, acupoint stimulation, and acupressure. Of the 24 randomized trials retrieved by a search of articles indexed on the MEDLINE and EMBASE databases (1980-1997), 19 were eligible for meta-analysis. The primary outcomes were the incidence of nausea, vomiting, or both 0-6 h (early efficacy) or 0-48 h (late efficacy) after surgery. The pooled relative risk (RR) and numbers needed to treat (NNT) were calculated. In children, no benefit was found. Some results in adults were significant. Nonpharmacologic techniques were similar to antiemetics in preventing early vomiting (RR = 0.89 [95% confidence interval 0.47-1.67]; NNT = 63 [10-infinity]) and late vomiting (RR = 0.80 [0.35-1.81]; NNT = 25 [5-infinity]) in adults. Nonpharmacologic techniques were better than placebo at preventing early nausea (RR = 0.34 [0.20-0.58]; NNT = 4 [3-6]) and early vomiting in adults (RR = 0.47 [0.34-0.64]; NNT = 5 [4-8]). Nonpharmacologic techniques were similar to placebo in preventing late vomiting in adults (RR = 0.81 [0.46-1.42]; NNT = 14 [6-infinity]). Using nonpharmacologic techniques, 20%-25% of adults will not have early PONV compared with placebo. It may be an alternative to receiving no treatment or first-line antiemetics. IMPLICATIONS: This systematic review showed that nonpharmacologic techniques were equivalent to commonly used antiemetic drugs in preventing vomiting after surgery. Nonpharmacologic techniques were more effective than placebo in preventing nausea and vomiting within 6 h of surgery in adults, but there was no benefit in children.

McQuay, H. J.; Moore, R. A. (1998): Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review. In: Health technology assessment, Jg. 2, H. 12, S. 1–236.

Abstract   BACKGROUND: Day-case surgery is of great value to patients and the health service. It enables many more patients to be treated properly, and faster than before. Newer, less invasive, operative techniques will allow many more procedures to be carried out. There are many elements to successful day-case surgery. Two key components are the effectiveness of the control of pain after the operation, and the effectiveness of measures to minimise postoperative nausea and vomiting. OBJECTIVES: To enable those caring for patients undergoing day-case surgery to make the best choices for their patients and the health service, this review sought the highest quality evidence on: (1) the effectiveness of the control of pain after an operation; (2) the effectiveness of measures to minimise postoperative nausea and vomiting. METHODS: Full details of the search strategy are presented in the report. RESULTS ANALGESIA: The systematic reviews of the literature explored whether different interventions work and, if they do work, how well they work. A number of conclusions can be drawn. RESULTS-ANALGESIA, INEFFECTIVE INTERVENTIONS: There is good evidence that some interventions are ineffective. They include: (1) transcutaneous electrical nerve stimulation in acute postoperative pain; (2) the use of local injections of opioids at sites other than the knee joint; (3) the use of dihydrocodeine, 30 mg, in acute postoperative pain (it is no better than placebo). RESULTS-ANALGESIA, INTERVENTIONS OF DOUBTFUL VALUE: Some interventions may be effective but the size of the effect or the complication of undertaking them confers no measurable benefit over conventional methods. Such interventions include: (1) injecting morphine into the knee joint after surgery: there is a small analgesic benefit which may last for up to 24 hours but there is no clear evidence that the size of the benefit is of any clinical value; (2) manoeuvres to try and anticipate pain by using pre-emptive analgesia; these are no more effective than standard methods; (3) administering non-steroidal antiinflammatory drugs (NSAIDs) by injection or per rectum in patients who can swallow; this appears to be no more effective than giving NSAIDs by mouth and, indeed, may do more harm than good; (4) administering codeine in single doses; this has poor analgesic efficacy. RESULTS-ANALGESIA, INTERVENTIONS OF PROVEN VALUE: These include a number of oral analgesics including (at standard doses): (1) dextropropoxyphene; (2) tramadol; (3) paracetamol; (4) ibuprofen; (5) diclofenac. Diclofenac and ibuprofen at standard doses give analgesia equivalent to that obtained with 10 mg of intramuscular morphine. Each will provide at least 50% pain relief from a single oral dose in patients with moderate or severe postoperative pain. Paracetamol and codeine combinations also appear to be highly effective, although there is little information on the standard doses used in the UK. The relative effectiveness of these analgesics is compared in an effectiveness ‘ladder’ which can inform prescribers making choices for individual patients, or planning day-case surgery. Dose-response relationships show that higher doses of ibuprofen may be particularly effective. Topical NSAIDs (applied to the skin) are effective in minor injuries and chronic pain but there is no obvious role for them in day-case surgery. RESULTS-POSTOPERATIVE NAUSEA AND VOMITING: The proportion of patients who may feel nauseated or vomit after surgery is very variable, despite similar operations and anaesthetic techniques. Systematic review can still lead to clear estimations of effectiveness of interventions. Whichever anti-emetic is used, the choice is often between prophylactic use (trying to prevent anyone vomiting) and treating those people who do feel nauseated or who may vomit. Systematic reviews of a number of different anti-emetics show clearly that none of the anti-emetics is sufficiently effective to be used for prophylaxis. (ABSTRACT TRUNCATE

Mollon, Brent; da Silva, Vitor; Busse, Jason W.; Einhorn, Thomas A.; Bhandari, Mohit (2008): Electrical stimulation for long-bone fracture-healing: a meta-analysis of randomized controlled trials. In: The Journal of bone and joint surgery. American volume, Jg. 90, H. 11, S. 2322–2330.

Abstract   BACKGROUND: Bone stimulation represents a $500 million market in the United States. The use of electromagnetic stimulation in the treatment of fractures is common; however, the efficacy of this modality remains uncertain. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of electromagnetic stimulation on long-bone fracture-healing. METHODS: We searched four electronic databases (MEDLINE, EMBASE, CINAHL, and all Evidence-Based Medicine Reviews) for trials of electromagnetic stimulation and bone repair, in any language, published from the inception of the database to April 2008. In addition, we searched by hand seven relevant journals published between 1980 and April 2008 and the bibliographies of eligible trials. Eligible trials enrolled patients with long-bone lesions, randomly assigned them to electromagnetic stimulation or a control group, and reported on bone-healing. Information on the methodological quality, stimulation device, duration of treatment, patient demographics, and all clinical outcomes were independently extracted by two reviewers. RESULTS: Of 2546 citations obtained in the literature search, eleven articles met the inclusion criteria. Evidence from four trials reporting on 106 delayed or ununited fractures demonstrated an overall nonsignificant pooled relative risk of 1.76 (95% confidence interval, 0.8 to 3.8; p = 0.15; I(2) = 60.4%) in favor of electromagnetic stimulation. Single studies found a positive benefit of electromagnetic stimulation on callus formation in femoral intertrochanteric osteotomies, a limited benefit for conservatively managed Colles fracture or for lower limb-lengthening, and no benefit on limb-length imbalance and need for reoperation in surgically managed pseudarthroses or on time to clinical healing in tibial stress fractures. Pain was reduced in one of the four trials assessing this outcome. CONCLUSIONS: While our pooled analysis does not show a significant impact of electromagnetic stimulation on delayed unions or ununited long-bone fractures, methodological limitations and high between-study heterogeneity leave the impact of electromagnetic stimulation on fracture-healing uncertain.

Mukaino, Yoshito; Park, Jongbae; White, Adrian; Ernst, Edzard (2005): The effectiveness of acupuncture for depression–a systematic review of randomised controlled trials. In: Acupuncture in medicine : journal of the British Medical Acupuncture Society, Jg. 23, H. 2, S. 70–76.

Abstract   OBJECTIVE: To summarise the existing evidence on acupuncture as a therapy for depression. METHODS: RCTs were included, in which either manual acupuncture or electroacupuncture was compared with any control procedure in subjects with depression. Data were extracted independently by two authors. The methodological quality was assessed. Pre and post means and SDs for depression specific measures were extracted, when available, for meta-analysis. RESULTS: Seven randomised comparative trials involving 509 patients were included. The evidence is inconsistent on whether manual acupuncture is superior to sham, and suggests that acupuncture was not superior to waiting list. Evidence suggests that the effect of electroacupuncture may not be significantly different from antidepressant medication, weighted mean difference -0.43(95% CI -5.61 to 4.76). There is inconclusive evidence on whether acupuncture has an additive effect when given as an adjunct to antidepressant drugs. CONCLUSION: The evidence from controlled trials is insufficient to conclude whether acupuncture is an effective treatment for depression, but justifies further trials of electroacupuncture.

Nnoaham, Kelechi E.; Kumbang, Jharna (2008): Transcutaneous electrical nerve stimulation (TENS) for chronic pain. In: Cochrane database of systematic reviews, H. 3, S. CD003222

Abstract         Nnoaham and Kumbang (2008) investigated the sole application of transcutaneous electrical nerve stimulation for chronic pain as part of a Cochrane project. The authors identified 124 studies; 99 did not meet the inclusion criteria. Twenty five (25) randomized controlled studies with more than 1200 participants were evaluated. The analysis showed that the majority of the studies demonstrated a positive impact on pain. A difference between high frequency and low frequency TENS could not be shown.

Proctor, M. L.; Smith, C. A.; Farquhar, C. M.; Stones, R. W. (2002): Transcutaneous electrical nerve stimulation and acupuncture for primary dysmenorrhoea. In: Cochrane database of systematic reviews, H. 1.

Abstract   BACKGROUND: Dysmenorrhoea is the occurrence of painful menstrual cramps of the uterus. Medical therapy for dysmenorrhoea commonly consists of nonsteroidal anti-inflammatory drugs or the oral contraceptive pill both of which work by reducing myometrial (uterine muscle) activity. However, these treatments are accompanied by a number of side effects, making an effective non-pharmacological method of treating dysmenorrhoea of potential value. Transcutaneous electrical nerve stimulation (TENS) is a treatment that has been shown to be effective for pain relief in a variety of conditions. Electrodes are placed on the skin and electric current applied at different pulse rates (frequencies) and intensities is used to stimulate these areas so as to provide pain relief. In dysmenorrhoea. TENS is thought to work by alteration of the body’s ability to receive or perceive pain signals rather than by having a direct effect on the uterine contractions. Acupuncture may also be indicated as a useful, non-pharmacological method for treating dysmenorrhoea. Acupuncture is thought to excite receptors or nerve fibres which, through a complicated interaction with mediators such as serotonin and endorphins, blocks pain impulses. Acupuncture typically involves penetration of the skin by fine, solid metallic needles, which are manipulated manually or by electrical stimulation. OBJECTIVES: To determine the effectiveness of high and low frequency transcutaneous electrical nerve stimulation and acupuncture when compared to each other, placebo, no treatment, or medical treatment for primary dysmenorrhoea. SEARCH STRATEGY: Electronic searches of the Cochrane Menstrual Disorders and Subfertility Group Register of controlled trials, CCTR (Cochrane Library Issue 3, 2001), MEDLINE, EMBASE, CINAHL, Bio extracts, PsycLIT and SPORTDiscus were performed in August 2001 to identify relevant randomised controlled trials (RCTs). The Cochrane Complementary Medicine Field’s Register of controlled trials (CISCOM) was also searched. Attempts were also made to identify trials from the UK National Research Register, the Clinical Trial Register and the citation lists of review articles and included trials. In most cases, the first or corresponding author of each included trial was contacted for additional information. SELECTION CRITERIA: The inclusion criteria were randomised controlled trials of transcutaneous electrical nerve stimulation and acupuncture that compared these treatments to each other, placebo, no treatment, or medical treatment for primary dysmenorrhoea. Exclusion criteria were: mild, infrequent or secondary dysmenorrhoea and dysmenorrhoea associated with an IUD. DATA COLLECTION AND ANALYSIS: Nine RCTs were identified that fulfilled the inclusion criteria for this review, seven involving TENS, one acupuncture, and one both treatments. Quality assessment and data extraction were performed independently by two reviewers. Meta analysis was performed using odds ratios for dichotomous outcomes and weighted mean differences for continuous outcomes. Data unsuitable for meta-analysis was reported as descriptive data and was also included for discussion. The outcome measures were pain relief (dichotomous, visual analogue scales, descriptive), adverse effects, use of analgesics additional to treatment and absence from work or school. MAIN RESULTS: Overall high frequency TENS was shown to be more effective for pain relief than placebo TENS. Low frequency TENS was found to be no more effective in reducing pain than placebo TENS. There were conflicting results regarding whether high frequency TENS is more effective than low frequency TENS. One small trial showed acupuncture to be significantly more effective for pain relief than both placebo acupuncture and two no treatment control groups. REVIEWER’S CONCLUSIONS: High frequency TENS was found to be effective for the treatment of dysmenorrhoea by a number of small trials. The minor adverse effects reported in one trial requires further investigation. There is insufficient evidence to determine the effectiveness of low frequency TENS in reducing dysmenorrhoea. There is also insufficient evidence to determine the effectiveness of acupuncture in reducing dysmenorrhoea, however a single small but methodologically sound trial of acupuncture suggests benefit for this modality.

Robb; Oxberry; Bennett; Johnson; Simpson; Searle (2008): A Cochrane Systematic Review of Transcutaneous Electrical Nerve Stimulation for Cancer Pain. In: Journal of pain and symptom management.

Abstract   Cancer-related pain is complex and multi-dimensional; yet, the mainstay of cancer pain management has been the biomedical approach. There is a need for nonpharmacological and innovative pain management strategies. Transcutaneous electrical nerve stimulation (TENS) may have a role. The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED, and PEDro databases were searched for randomized controlled trials (RCTs) investigating the use of TENS for the management of cancer-related pain in adults. Once relevant studies were identified, two pairs of reviewers assessed eligibility for inclusion in the review based on a study eligibility form and using the 5-point Oxford Quality Scale. Two RCTs met the study eligibility criteria (these involved 64 patients). These studies were heterogeneous with respect to study population, methodology, and outcome measures. This prevented meta-analysis. In one RCT, there were no significant differences between TENS and placebo in women with chronic pain secondary to breast cancer treatment. In the other RCT, there were no significant differences between acupuncture-like TENS (AL-TENS) and sham in palliative care patients; this study was significantly underpowered. There is insufficient available evidence to determine the effectiveness of TENS in treating cancer-related pain. Further research is needed to help guide clinical practice, and large multi-center RCTs are required to assess the value of TENS in the management of cancer-related pain in adults.

Robb, Karen A.; Bennett, Michael I.; Johnson, Mark I.; Simpson, Karen J.; Oxberry, Stephen G. (2008): Transcutaneous electric nerve stimulation (TENS) for cancer pain in adults. In: Cochrane database of systematic reviews, H. 3.

Abstract   BACKGROUND: Cancer-related pain is complex and multi-dimensional but the mainstay of cancer pain management has predominately used a biomedical approach. There is a need for non-pharmacological and innovative approaches. Transcutaneous Electric Nerve Stimulation (TENS) may have a role for a significant number of patients but the effectiveness of TENS is currently unknown. OBJECTIVES: The aim of this systematic review was to determine the effectiveness of TENS for cancer-related pain in adults. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, CINAHL, PsychINFO, AMED and PEDRO databases (11/04/08). SELECTION CRITERIA: Only randomised controlled trials (RCTS) investigating the use of TENS for the management of cancer-related pain in adults were included. DATA COLLECTION AND ANALYSIS: The search strategy identified 37 possible published studies which were divided between two pairs of review authors that decided on study selection. A study eligibility form was used to screen each abstract and where study eligibility could not be determined from the abstract, the full paper was obtained and assessed by one pair of review authors. A standardised data extraction sheet was used to collect information on the studies and the quality of the studies was assessed independently by two review authors using the validated five-point Oxford Quality Scale. Final scores were discussed and agreed between all four review authors. The small sample sizes and differences in patient study populations of the two included studies prevented meta-analysis. MAIN RESULTS: Only two RCTs met the eligibility criteria (64 participants). These studies were heterogenous with respect to study population, sample size, study design, methodological quality, mode of TENS, treatment duration, method of administration and outcome measures used. In one RCT, there were no significant differences between TENS and placebo in women with chronic pain secondary to breast cancer treatment. In the other RCT, there were no significant differences between acupuncture-type TENS and sham in palliative care patients; this study was underpowered. AUTHORS’ CONCLUSIONS: The results of this systematic review are inconclusive due to a lack of suitable RCTs. Large multi-centre RCTs are required to assess the value of TENS in the management of cancer-related pain in adults.

Shiao, Shyang-Yun Pamela K; Dibble, Suzanne L. (2006): Metaanalyses of acustimulation effects on nausea and vomiting across different patient populations: a brief overview of existing evidence. In: Explore, Jg. 2, H. 3, S. 200–201.

Shiao, Shyang-Yun Pamela K; Dune, Linda S. (2006): Metaanalyses of acustimulations: effects on nausea and vomiting in postoperative adult patients. In: Explore, Jg. 2, H. 3, S. 202–215.

Abstract   OBJECTIVE: Using metaanalysis to examine the effects of acustimulations on nausea and vomiting symptoms (NVS) in postoperative adult populations. METHODS: Metaanalyses of effects of various acupoints stimulations (AS) (including acupuncture, acupressure, and electrical stimulation) on NVS in postoperative adult populations were performed. Thirty-three quality randomized controlled trials (RCT) published over the past three decades were identified by evaluating the quality of randomization and treatment methods, and results were pooled using a fixed effects model. RESULTS: Twenty-four trials were pooled for nausea, 29 trials for vomiting, and 19 trials for rescue antiemetics, with AS compared with placebo or controls. Two additional trials did not have control groups but compared AS to medication groups. Compared with the controls, AS (all modalities) reduced nausea (relative risk [RR] = 0.60, 95% confidence interval [CI]: 0.54-0.67, P < .0001), vomiting (RR = 0.51, 95% CI: 0.45-0.57, P < .0001), and use of rescue antiemetics (RR = 0.63, 95% CI: 0.54-0.74, P < 0001). All AS modalities were effective in reducing NVS. Korean hand acupressure stimulations (two trials) had the best impact on reducing vomiting. There were no significant differences on pooled RRs for nausea (five trials) and vomiting (eight trials) between medication and AS groups, but medication groups had increased use of rescue antiemetics (two trials, RR = 2.27, 95% CI: 1.48-3.49, P = .0002). There was a placebo effect when compared with controls in reducing nausea (four trials, RR = 0.67, 95% CI: 0.50-0.90, P = .0069) and vomiting (three trials, RR = 0.39, 95% CI: 0.19-0.80, P = .0106). CONCLUSIONS: This metaanalysis demonstrated that AS is just as effective as medications in reducing NVS and that acupressure is just as effective as acupuncture or electrical stimulation in reducing NVS for postoperative adult populations.

Shiflett, Samuel C. (2007): Does acupuncture work for stroke rehabilitation: what do recent clinical trials really show. In: Topics in stroke rehabilitation, Jg. 14, H. 4, S. 40–58.

Abstract   A number of randomized controlled trials of acupuncture for stroke recovery were critically reviewed, beginning with an existing systematic review and meta-analysis. A number of these clinical studies suffered from methodological flaws that tended to obscure and reduce the reported effect size. These flaws included inadequate statistical analysis, failure to adequately account for differences in baseline stroke severity, and the use of an inadequate posttreatment assessment period. These three flaws, taken individually or in combination, resulted in the underreporting of acupuncture effects in 5 of the randomized controlled trials reviewed. By informally adjusting study results for these limitations, it was possible to demonstrate that acupuncture is probably much more effective in assisting stroke recovery than has generally been reported, especially when the stroke is in the moderately severe range. The negative impact of well-intended but inappropriate exclusion criteria in the meta-analysis was also illustrated. The importance of giving more attention to ancillary results, such as walking speed and mortality, was illustrated as a way to gain a deeper understanding of the true impact of a still poorly understood therapy such as acupuncture. The general conclusion of the reanalysis presented here is that there is in fact substantial evidence that acupuncture is effective as an adjunctive treatment for facilitating stroke recovery.

Sulkes, Aaron (2002): [The use of adjuvant chemotherapy in stage II breast cancer in the last 25 years–a brief review]. In: Harefuah, Jg. 141, H. 4, S. 374-8, 408.

Abstract   This review summarizes more than 25 years of experience with the use of systemic chemotherapy in the adjuvant setting in patients suffering from stage II breast cancer. The use of the CMF combination in the early 70’s marks the onset of the modern era of this modality. Adjuvant chemotherapy must be given at optimal doses and schedule, usually for a period lasting about six months, beginning shortly after the resection of the primary tumor. The incorporation of the anthracyclines, adriamycin and epirubicin represent an important milestone in the developmental history of the adjuvant chemotherapy of breast cancer. The sequential administration of adriamycin followed by CMF in patients with 4 or more involved axillary lymph nodes deserves particular emphasis. Meta-analysis of multiple clinical trials including several tens of thousands of patients with stage II breast cancer indicate that adjuvant chemotherapy results in a significant increase in both recurrence-free and overall survival as compared to locoregional treatment only. This holds true with long-term follow-up of 20 years and more as illustrated by the CMF experience, showing about a 35% decrease in the relative risk of recurrence. Efforts in recent years are investigating the role of newer cytotoxic agents such as the taxanes in the adjuvant setting. Furthermore, clinical trials are now ongoing with the use of the monoclonal antibody herceptin in patients with stage II breast cancer whose tumor over-expresses the oncogene Her2neu. The administration of adjuvant chemotherapy has the potential for undesirable side effects such as an increased risk of osteoporosis and ischemic heart disease in younger patients in whom amenorrhea develops, or cardiotoxicity from anthracyclines. Most clinical trials to date have not shown an increase in the occurrence of second primary tumors among patients receiving adjuvant chemotherapy for breast cancer. Adjuvant chemotherapy has become an integral part of the treatment of stage II breast cancer.

Tamaoki, Toshio; Motohashi, Nobutaka (2007): [Other treatments for depressive patients]. In: Nippon rinsho. Japanese journal of clinical medicine, Jg. 65, H. 9, S. 1655– 1659.

Abstract   Electroconvulsive therapy(ECT) is one of the most important methods in treating depressive patients especially who can not be improved with medication. Meta analysis shows that ECT is superior to pharmacotherapy as acute treatment for depression. ECT was invented in 1938, and it took some improvement afterwards such as development of modified ECT and introduction of brief-pulse stimulation for the purpose of reducing adverse effects. However, adverse effects such as cognitive impairment are not completely solved, and some patients do not respond to ECT. Transcranial magnetic stimulation (TMS), vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are under investigation to get over the shortcomings of ECT.

White, A. R.; Resch, K. L.; Ernst, E. (1998): Randomized trial of acupuncture for nicotine withdrawal symptoms. In: Archives of internal medicine, Jg. 158, H. 20, S. 2251–2255.

Abstract   BACKGROUND: Acupuncture is frequently used for smoking cessation. Positive results from uncontrolled studies have not been supported by metaanalysis of controlled trials. One possible reason for this is that the optimal acupuncture technique was not applied or that the technique was not repeated sufficiently often. METHODS: A randomized, sham-controlled trial was performed with 2 parallel treatment arms; the participant and the evaluator were unaware of which treatment was received. Seventy-six adults who wanted to stop smoking received either 100-Hz electroacupuncture with needles inserted into the appropriate point in each ear or a sham control procedure over the mastoid bone. Interventions were given on days 1, 3, and 7 of smoking cessation. Nicotine withdrawal symptoms were measured by visual analog scale scores recorded in a daily diary for 14 days; smoking cessation was confirmed objectively. RESULTS: There was no significant difference between the mean reduction of withdrawal symptom scores of the 2 groups from day 1 to day 14. Fifteen participants (39%) who received electroacupuncture and 16 participants (42%) who received a sham procedure were abstinent on day 14. CONCLUSION: This form of electroacupuncture is no more effective than placebo in reducing nicotine withdrawal symptoms.

8.2       List of Abbreviations