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. 2001 Jul 16;1:3. doi: 10.1186/1472-6882-1-3

Systematic reviews of complementary therapies - an annotated bibliography. Part 1: Acupuncture

Klaus Linde 1,2,✉, Andrew Vickers 3, Maria Hondras 4, Gerben ter Riet 5,6, Johannes Thormählen 1, Brian Berman 7, Dieter Melchart 1
PMCID: PMC37539  PMID: 11513758

Abstract

Background

Complementary therapies are widespread but controversial. We aim to provide a comprehensive collection and a summary of systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, homeopathy). This article is dealing with acupuncture. Potentially relevant reviews were searched through the register of the Cochrane Complementary Medicine Field, the Cochrane Library, Medline, and bibliographies of articles and books. To be included articles had to review prospective clinical trials of acupuncture; had to describe review methods explicitly; had to be published; and had to focus on treatment effects. Information on conditions, interventions, methods, results and conclusions was extracted using a pretested form and summarized descriptively.

Results

From a total of 48 potentially relevant reviews preselected in a screeening process 39 met the inclusion criteria. 22 were on various pain syndromes or rheumatic diseases. Other topics addressed by more than one review were addiction, nausea, asthma and tinnitus. Almost unanimously the reviews state that acupuncture trials include too few patients. Often included trials are heterogeneous regarding patients, interventions and outcome measures, are considered to have insufficient quality and contradictory results. Convincing evidence is available only for postoperative nausea, for which acupuncture appears to be of benefit, and smoking cessation, where acupuncture is no more effective than sham acupuncture.

Conclusions

A large number of systematic reviews on acupuncture exists. What is most obvious from these reviews is the need for (the funding of) well-designed, larger clinical trials.

Background

Complementary therapies are widely used throughout the world [1,2,3] but their effectiveness is controversial. Although these therapies are clearly under-researched compared to their relevance in actual care, the total number of clinical trials in many areas is considerable [4]. There is a need to know what evidence is available and which questions have not yet been addressed. Systematic reviews are considered to be the best available method to this end [5]. In recent years an increasing number of such reviews has been performed in a variety of complementary therapies. The objective of our series of reports is to provide a comprehensive collection and transparent summary of the available systematic reviews of clinical trials in three major complementary therapies (acupuncture, herbal medicine, and homeopathy). It was not our primary objective to assess efficacy as we do not consider a review of reviews of a large number of interventions an appropriate tool for this purpose. However, when summarizing the results of systematic reviews it is unavoidable to cite their conclusions on efficacy. Our results are presented in three consecutive articles. This first article deals with acupuncture.

Acupuncture is a therapy that involves the stimulation of defined points on the skin typically by inserting needles; however, related techniques such as manual (acupressure), electrical or laser stimulation of acupuncture points are also often summarised under this term [6,7]. Acupuncture is, together with the use of herbal medicines and other treatment modalities, a part of traditional Chinese medicine. In the West it is often used as a single therapy. The basic idea underlying acupuncture is that disorders related to the flow of Chi (the traditional Chinese concept translated as vital force or energy) can be prevented or treated by stimulating the relevant points on the body surface.

Methods

To be included in this overview reviews had to meet the following criteria: 1) Report reviews prospective (not necessarily controlled) clinical trials of acupuncture or related methods (such as acupressure) in humans. 2) Reports explicitly describe, at least, one of the following issues: a) methods for searching primary studies and eligibility criteria for primary studies; b) methods to assess quality aspects; c) methods to summarise the results of the primary studies. 3) Reports are published in journals, books, theses, or the internet. Reviews published before 1989 and as abstracts only were not included. 4) The primary focus of the report is on treatment effects (not diagnosis, side effects, risks, etc.). There were no language restrictions. Disease-oriented reviews including a variety of interventions were included only if they reviewed at least 4 acupuncture trials.

The primary source for identification of systematic reviews was the register of the Cochrane Complementary Medicine Field. For the compilation of this register a variety of databases including Medline, Embase, CISCOM, AMED and other sources have been searched. In addition, we searched 1) Medline 1989 to July 2000 using a standard strategy to identify systematic reviews [8] (see strategy list) combined with the terms acupuncture or acupressure; and 2) the Cochrane Library (last check in issue 2000, 3). Bibliographies of articles obtained and relevant textbooks were screened for further potentially relevant articles. The literature list from the Complementary Medicine Field register was screened in a first step independently by two reviewers who excluded all references for which they were sure that the papers were not systematic reviews. Abstracts of the publications identified by other means were screened by one reviewer. Full copies were obtained for all potentially relevant papers. One (in 46% of papers), two (53%) or three (1%) reviewers checked eligibility and extracted information (bibliographic details, topic, intervention, inclusion criteria, methodological issues, studies and number of patients included, results, and conclusions) from included reviews using pretested forms. For this report the included reviews were summarised in a tabular format giving basic information on the conditions, interventions, comparisons, number of studies reviewed, methodological features, results, and conclusions drawn by the reviewers (if possible in the original wording). We assessed the following methodological features: Comprehensiveness of the literature search (scored if in addition to Medline other databases and non-electronic sources were searched), whether inclusion and exclusion criteria were explicitly listed, whether the quality of primary studies was assessed using fomal methods (such as scores or checklists), whether a summary of results was provided for each included study, and whether a quantitative meta-analysis was performed.

If several review publications by the same team of reviewers with the same focus and published within a time span of 3 years were available these were considered as updates unless inclusion criteria for the two versions were clearly different.

Strategy to search systematic reviews in the Medline database(Ovid Version)[8]

#1 systematic adj reviews.tw.

#2 data adj synthesis.tw.

#3 published adj studies.ab.

#4 data adj extraction.ab.

#5 meta-analysis/

#6 meta analysis.ti.

#7 comment.pt

#8 letter.pt.

#9 editorial.pt.

#10 animal/

#11 human

#12 10 not (10 and 11)

#13 search terms for specific therapy

#14 13 not (7 or 8 or 9 or 12)

#15 or/1-6

#16 14 and 15

Results

From a total of 48 potentially relevant reviews preselected through the screening process, 39 (published in 45 papers) met the inclusion criteria [9-53]. Five reviews were excluded as they were not truly systematic reviews (not meeting inclusion criterion 2) [54-58] and 4 as they did not focus on treatment effects but on methodological issues [59-62].

As expected, many reviews addressed pain (see table 1). Three reviews (published 1989 [10,12], 1990 [11] and 2000 [9]) focused on chronic pain. The study samples (total number of trials covered in any of the reviews 72) and review methods differed considerably among the reviews but all agreed that the available evidence is inconclusive. Back and neck pain were addressed in six reviews (total number of trials covered for each back and neck pain 11). Conclusions regarding back pain were contradictory [13,15-19] while the evidence regarding neck pain was considered inconclusive [13,14]. Six reviews addressed various types of headaches (total number of trials covered 25). The largest review which focused on migraine and tension-type headache [21] drew tentatively positive conclusions. The remaining reviews included fewer studies and the evidence was considered inconclusive [20,[22-25]].

Table 1.

Systematic reviews of clinical trials of acupuncture & acupressure in pain

Author Year Indication Controls Studies features Results Conclusion
1 / 2 / 3
/ 4 / 5
Chronic
pain
Ezzo 2000 chronic sham, 51 RCT y / y / y / Positive results in 21 studies, negative in 3, Limited evidence that acupuncture is
[9] pain placebo, no y / n and neutral in 27. Better studies more often more effective than no treatment,
treatment, negative or neutral inconclusive evidence regarding
standard placebo, sham and standard care
ter Riet chronic sham, 51 CCT y / y / y / Trials small and of low quality. 24 with The efficacy of acupuncture in the
90/89 pain other, no y / n positive and 27 with negative results. Better treatment of chronic pain remains
[10,11] treatment studies more often negative doubtful
Patel 89 [12] chronic sham, no 14 RCT n / y / n Overall patients receiving acupuncture were Available evidence positive but
pain treatment, / y / y 18% (p < 0.01) more likely to experience definitive conclusions difficult due to
standard improvement various potential sources of bias
Smith 2000 back & sham, 13 RCT y / y / y / 5 studies positive, 8 studies negative; better No convincing evidence for the
[13] neck pain other, no y / n studies reported more often negative results analgetic efficacy of acupuncture for
treatment back and neck pain
White 99 neck pain sham, 14 RCT y / y / y / 7 studies positive, 7 negative. Of the 8 better No convincing evidence for the
[14] other, no y / n studies 5 negative, 3 positive effectiveness of acupuncture for neck
treatment pain
van Tulder low back sham, 11 RCT y / y / y / Conclusions of primary authors positive in 8 Authors would not recommend acu-
99 [15,16] pain other, no y / n studies, by reviewers for 2 studies. puncture as regular treatment for low
treatment Methodological quality judged as low back pain. High quality trials needed
Ernst 98 [17] back pain sham, 12 RCT y / y / y / OR for improvement compared with all Acupuncture superior to various
other, no y / y control interventions 2.30 (95%CI 1.28–4.13), control interventions although
treatment with sham 1.37 (0.84–2.25). Majority of insufficient evidence whether
studies good quality superior to sham
Longworth sciatica unclear 1 RCT, 6 p / p / n Most studies of poor quality; a large number There may be a role for acupuncture
97 [18] CCT, 31 / y / n of patients seem to have benefited treatment of lumbar disk protrusions
uncontrolled and sciatica
studies
ter Riet 89 neck and unclear 16 RCT, 6 y / p / y Study design was generally poor. Results Due to the low methodological quality
[19] back pain CCT / n / n only discussed for a few better quality no definitive conclusions can be
studies drawn
Headache
McCrory tension- sham, 6 RCT y / y / y / 3 of 4 sham-controlled trials positive (best Insufficient evidence to draw
2000* [20] type physio- y / n negative), physiotherapy better in 1 of 2 trials conclusions on the efficacy. Further
headache therapy rigorous trials needed
Melchart 99 idiopathic sham, 22 RCT y / y / y / Majority of 14 sham controlled trials with at Existing evidence suggests that
[21] headaches other, no y / y least a trend in favour of acupuncture. Trials acupuncture has a role in headache
treatment vs. other treatments contradictory treatment. However, quality and
amount of evidence not fully
convincing
Goslin 99 migraine sham, 6 RCT y / y / y / 2 of 3 placebo-controlled trials positive, Insufficient data on acupuncture to
[22] other, no y / n similar effects as drug treatment in 2 trials draw conclusions on its efficacy
treatment
Vernon 99** tension- sham, 8 RCT y / y / y / 2 of 4 sham-controlled trials positive, results Too few trials and contradictory
[23] type and other, no y / n vs. physiotherapy contradictory findings precluding definitive
cervicogeni treatment conclusions
c
ter Riet 89 tension sham, other 7 RCT, 1 y / p / y Small study size and methodological No definitive conclusions on the
[24] type treatment CCT / n / n problems make the available trials effectiveness of acupuncture for
headache uninterpretable headache can be drawn
ter Riet 89 facial pain sham 2 RCT y / p / y Methodological quality poor No definitive conclusions possible
[25] / y / n
Pain
various
Ernst 98 [26] acute sham, 11 RCT, 5 y / p / y The majority of trials imply that acupuncture Acupuncture can alleviate dental pain
dental pain other, no CCT / y / n is effective in dental analgesia but additional research necessary
treatment
Ernst 99 [27] temporoma other and 3 RCT y / y / n 3 comparisons with standard treatments and Available data suggest beneficial
n-dibular no / y / n 2 with no treatment with favorable effects of effects; more rigorous, sham-
joint treatment acupuncture controlled trials needed
dysfunction
Open in a new tab

*Disease focused review on a variety of interventions including acupunture and acupressure; **Disease focused review on a variety of complementary medicine interventions including acupunture and acupressure Features: 1 = comprehensive search, 2 = explicit inclusion criteria, 3 = formal quality assessment, 4 = summary of results for each included study, 5 = meta-analysis; y = yes, p = partly, n = no, - = not applicable, ? = unclear RCT = randomized controlled trials, CCT = non-randomized controlled trials, CS = cohort studies; OR = odds ratio, RR = rate ratio

The available trials suggest that acupuncture is effective in postoperative pain after dental treatment and temporomandibular dysfunction although further research is still considered necessary [26,27,53].

Systematic reviews of acupuncture and acupressure for rheumatic diseases, addiction, nausea and asthma are summarized in table 2. A variety of rheumatic conditions has been addressed in five reviews. The limited evidence available so far suggests that acupuncture may have favorable effects in fibromyalgia [28]. The majority of the available trials on osteoarthritis report improvement with both sham and true acupuncture but no significant differences between the two [29]. For a variety of other rheumatoid diseases the evidence was considered inconclusive [30,31,32].

Table 2.

Systematic reviews of clinical trials of acupuncture & acupressure in rheumatic diseases, addiction, nausea and asthma

Feature
Author Year Indication Controls Studies s Results Conclusion
1 / 2 / 3
/ 4 / 5
Rheumatic diseases
Berman 99 fibromylgia sham, other 3 RCT, 3 CS y / y / y / Acupuncture more effective than sham for Limited amount of evidence positive.
[28] treatments y / n symptoms and global ratings Further research needed
Ernst 97 [29] osteoarthriti sham, other 13 RCT y / p / n Both sham and true acupuncture improve The notion that acupuncture is
s and no / y / n symptoms but better trials suggest no superior to sham-needling is not
treatment difference between the two supported by data from controlled
clinical trials
Lauten- inflammator sham, no 2 RCT, 7 n / p / n Controlled trials contradictory, quality often Acupuncture cannot be
schläger 97 y treatment, CCT, 9 CS / y / n low recommended for rheumatoid
[30] rheumatoid other acup. arthritis, spondarthropathy, lupus
diseases eryth., sclerodermia
Jacobs 91** rheumatic sham, other 23 CCT p / y / n 7 trials positive, 13 trials no effect over No specific conclusion on
[31] diseases treatment / y / n placebo or control, 3 trials unclear acupuncture (generally: no
convincing evidence for alternative
therapies in rheumat.)
ter Riet 89 rheumatoid sham 1 RCT, y / p / y Only 1 trial summarized; this found positive No definitive conclusions possible
[32] arthritis 2CCT / n / n effects on pain but not on inflammation
Addiction
White smoking sham, other 20 RCT y / y / y / Acupuncture vs. sham: OR for cessation There is no evidence for the specific
2000/99 cessation and no y / y 1.22 (95%CI 0.99–1.49) after treatment and effectiveness of acupuncture in
[33,34] treatment 1.02 (0.72–1.43) at 12 months. No difference smoking cessation greater than a
compared to other interventions, better than placebo effect
no treatment
White 97 smoking sham 7 RCT y / y / y / 6 of the 7 studies do not yield cessation rates Acupuncture for smoking cessation
[35] cessation y / n that are significantly different from sham does not produce an effect greater
acupuncture than placebo
Law 95* [36] smoking sham, other 8 RCT p / p / n Compared to control 3% (95%CI -1 to 6%) Acupuncture is ineffective
cessation and no / n / y more participants stopped smoking with
treatment acupuncture
ter Riet A. smoking sham, other A. 13 RCT, 2 y / p / y A. 3 of 15 studies positive Claims that acupuncture is effective
90/89 [37,38 cessat. and no CCT / y / n for the treatment of tobacco, alcohol
39] B. alcohol treatment, B. 1RCT, 1 B. 2 of 2 studies positive and heroine addiction are not
addict. other acu CCT supported by sound clinical research
C. heroine C. 5 CCT C. 3 of 5 studies positive
addict.
Nausea
Lee 99 [40] postoperati sham, other 19 RCT y / p / y RR of early vomiting compared to Acupuncture equivalent to commonly
ve nausea and no / y / y antiemetics 0.89 (95%CI 0.47–1.67) and to used antiemetic drugs. More effective
(prevention) treatment placebo 0.47 (0.34–0.64), late vomiting 0.81 than placebo in first 6 h after surgery
(0.46–1.42) in adults but no benefit observed in
children
Aikins nausea in sham, no 7 RCT y / p / n 6 of 7 P6 acupressure trials positive, 1 trial Available evidence positive but
Murphy 99** pregnancy treatment / y / no on P6 electrical stimulation positive equivocal
[41]
Jewell 98* nausea in sham, no 4 RCT y / y / y / 3 of 4 P6 acupressure trials positive, 2 cross- Available evidence positive but
[42] early treatment y / y over trials excluded, best trial negative equivocal
pregnancy
Vickers 96 nausea in sham, other 33 CCT y / y / y / 27 of 33 trials positive, 11 of 12 sham- Except when administered under
[43] surgery, and no y / n controlled randomized trials positive anesthesia P6 acupuncture point
(stimulation pregnancy, treatment stimulation seems to be an effective
at point P6) chemother. antiemetic technic
Asthma
Linde 98 [44] asthma sham 7 RCT y / y / y / Highly heterogeneous trials; two positive, five It is not yet possible to make any
(acute y / p found no difference recommendations about the practice
attack trials of acupuncture in the treatment of
excl.) asthma
Linde 96 [45] asthma sham, no, 15 RCT y / y / y / Contradictory results, highly heterogeneous There is insufficient data to draw
other y / n trials reliable conclusions about the
treatment effectiveness of acupuncture for
asthma
Kleijnen 91 asthma unclear 9 RCT, 4 y / p / y Quality low, contradictory results Claims that acupuncture is effective
[46] & ter CCT / n / n in the treatment of asthma are not
Riet 89 [47] based on well performed clinical trials
Open in a new tab

legend see table 1

The trials on smoking cessation show in a fairly consistent manner that acupuncture does not seem to have lasting effects over sham acupuncture [33-39] (total number of trials covered 22). The only identified review on alcohol and heroin addiction which met our inclusion criteria was published in 1989 [39]; several narrative reviews including new trials on the topic are available (for example [55]).

Trials on nausea are unique in acupuncture research as they focus almost completely on acupuncture or acupressure at a single point (P6). There is good evidence that both acupuncture and acupressure are effective in postoperative nausea (total number of trials covered 24) while the results are equivocal for early morning sickness [40-43] (total number of trials covered 8). Most of the trials report positive results but a recent high quality trial could not replicate the findings [63]. Several studies suggest that stimulation of P6 is also effective in treating chemotherapy-induced nausea [43].

Results on asthma are contradictory and all available trials are very small [44-47] (total number of trials covered 15).

Systematic reviews of acupuncture and acupressure for a variety of additional conditions are summarized in table 3. While the findings of the available trials on tinnitus and weight reduction do not suggest important effects [48,49,50] a review on acupuncture as an adjunct treatment in stroke rehabilitation found promising results [51].

Table 3.

Systematic reviews of clinical trials of acupuncture & acupressure in various conditions

Feature
Author Year Indication Controls Studies s Results Conclusion
1 / 2 / 3
/ 4 / 5
Park 2000 tinnitus sham, other 6 RCT y / y / y / 2 unblinded studies positive whereas 4 No evidence from rigorous RCT that
[48] treatment y / n blinded studies showed no significant effects acupuncture has specific effects in
of acupunct. the treatment of tinnitus
Dobie 99 * tinnitus sham, other 6 RCT p / p / p No significant effects shown. Patients in No specific conclusions for
[49] treatment / p / n cross-over studies tend to prefer acupuncture drawn (generally: no
acupuncture treatment well established)
Ernst 97 [50] weight or sham 4 RCT ? / y / y Two studies positive effect mainly on Claims that acupuncture reduces
appetite / y / y appetite, two studies (better quality) negative weight or appetite not based on well-
reduction performed clinical trials
Ernst 96 [51] stroke no 5 RCT, 1 y / y / n All trials suggest positive effects on Evidence encouraging but not
rehabilitatio treatment CCT / y / n functional recovery; numerous compelling
n (routine methodological problems
only)
Harris 97 various sham, 23 clinical p / n / y P6 acupressure effective for nausea, other No clear conclusion beyond results
(only acu- other, no studies / n / n research scarce and low quality drawn
pressure) treatment
[52]
Rosted 98 dentistry sham, 15 RCT y / p / y Most studies with relevant methodological The value of acupuncture as an
[53] (mainly other, no / n / n problems. 11 of 15 trials with positive results analgesic must be questioned due to
temporoma treatment problems in the trials. But the effect
ndibular in temporomandibular dysfunction
dysfunction and facial pain seems real
)
Open in a new tab

legend see table 1

Finally, there is one review summarizing research on acupressure for various conditions (acceptable evidence only available for nausea [52]) and another on acupuncture in various conditions related to dentistry (reporting promising evidence for temporomandibular dysfunction [53]).

Discussion

Although a considerable number of clinical trials on acupuncture is available the evidence so far is very often inconclusive. Apart from postoperative nausea (positive) and smoking cessation (negative) the reviewers apparently felt unable to make clear conclusions whether acupuncture was effective or not. This finding is somewhat frustrating. The primary problem in acupuncture studies seems to be sample size (most studies are very small). For example, median sample sizes of trials in low back pain, headache and osteoarthirits were 50 [16], 37 [21] and 31 [29], respectively. A second relevant problem is methodological quality. There was an almost uniform call for large, well-designed studies. Why are so few such studies available?

One reason is probably the lack of funding for such studies. There is little industrial interest in acupuncture, so major funding has to come mainly from public resources. In several countries a limited number of larger studies (on low back pain [64] with planned 170 patients and on headache [65] with 300 patients in the UK funded by the NHS; and on osteoarthritis [personal communication, Brian Berman] with 570 patients in the US funded by the NIH) is now underway which might bring some advances. A second - partly related - reason is that a competent research infrastructure has been developed only very slowly. A third reason is that clinical research in acupuncture is difficult. Acupuncture (as other non-drug therapies like physiotherapy) is a term for describing a group of quite heterogeneous interventions. Some providers clearly find it misleading to include techniques without needling into systematic reviews of acupuncture while those who apply acupressure or laser acupuncture often hold the opinion that the crucial issue is the stimulation of the correct point no matter by which way. Acupuncture strategies for the treatment of a specific condition can be highly variable. Some acupuncturists use similar approaches in all patients with a given Western diagnosis while others consider this as inadequate and claim that the treatment has to be "individualized." This is often misunderstood: Patients with the same Western diagnosis get different treatment because they have different diagnoses according to traditional Chinese medicine which uses different disease groups. Furthermore, different schools of acupuncture exist within Western and more traditional approaches.

Another significant problem in acupuncture research is choosing appropriate placebo controls if the objective is to evaluate specific effects. Techniques applied include mock transcutaneous nerve stimulation, sham laser acupuncture, needling superficially, needling wrong or inadequate points etc. There is some evidence that different types of acupuncture "placebos" have different effects [59]. For example, techniques that involve needling (and which are less likely to be distinguishable and therefore are considered as better for blinding) can cause relevant physiological responses [66].

Several reviews described a negative correlation between study quality and outcome (better studies were more often negative; for example [9,11,13]). This finding has to be interpreted with caution. Many reviews included trials with very different control groups: waiting list or no treatment, the various "placebo" techniques listed above, and a variety of active controls. If acupuncture has at least some placebo effect, attributable to the psychological effects of being administered a novel therapy, one would expect placebo-controlled trials to show smaller differences between groups than trials without placebo control. Acupuncture trials without placebo control cannot be blinded and therefore typically score lower on quality scales. Given that links between study quality and outcome are confounded by the issues of non-specific effects, and given that trials with different control groups answer different questions, analyses checking the influence of quality aspects on outcomes should only be performed within groups of trials with comparable controls.

This annotated bibliography of systematic reviews should also be interpreted with great caution. The risk of oversimplification in a systematic review is great. In a review of reviews it is extreme. We summarise the conclusion of a systematic review in a single phrase. Clinical decisions for treatment of individual patients should not be based on our work. For this, patients and health care professionals have to turn to the original reviews. Our aim was to provide a clear summary of what is available and where further information can be found. We tried to be as comprehensive as possible in our search but cannot exclude that we have overlooked eligible work, particularly if this was not published in a journal.

Our findings are generally in accordance with those of a panel of the National Institutes of Health reporting on acupuncture in 1998 [67]. However, the conclusions of the panel that the evidence on acupuncture is promising for a variety of conditions but not conclusive seems slightly more optimistic than the picture which emerges from the available systematic reviews.

We did not systematically search the literature on systematic reviews of side effects of acupuncture. We came across one such review which had collected case reports [68]. However, for a reliable assessment of safety large scale prospective studies or effective surveillance systems are needed in addition.

In conclusion, while in some areas only older reviews are available and some minor topics are not reviewed at all it is obvious that what is needed is new primary research and not new systematic reviews. Future trials should have larger sample sizes, rigorous methods, and should reflect principles and practice of acupuncture as applied in actual practice. Until conclusive data becomes available we must be aware that most decisions in health care regarding acupuncture are based - as in many other areas of medicine - on partial evidence about which reasonable people can disagree.

Competing interest

KL, DM, GtR, BB and AV have been involved in some of the reviews analyzed. These were extracted and assessed by other members of the team.

Pre-publication history

The pre-publication history for this paper can be accessed here:

http://www.biomedcentral.com/content/backmatter/1472-6882-1-3-b1.pdf

Acknowledgments

Acknowledgements

KL's work was partly funded by the NIAMS grant 5 U24-AR-43346 -02 and by the Carl and Veronica Carstens Foundation, Essen, Germany.

Contributor Information

Klaus Linde, Email: Klaus.Linde@lrz.tu-muenchen.de.

Andrew Vickers, Email: vickersa@mskcc.org.

Maria Hondras, Email: mhondras@interaccess.com.

Gerben ter Riet, Email: G.terRiet@EPID.UNIMAAS.NL.

Johannes Thormählen, Email: Johannes.Thormaehlen@innovacare.de.

Brian Berman, Email: Bberman@compmed.ummc.umaryland.edu.

Dieter Melchart, Email: Dieter.Melchart@lrz.tu-muenchen.de.

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