Acupuncture for osteoarthritic pain: an observational study in routine care

Abstract

Objective. To investigate characteristics and outcomes of patients undergoing acupuncture treatment for osteoarthritic pain under conditions of routine care in the framework of statutory health insurance in Germany.

Methods. Patients with chronic pain due to osteoarthritis (ICD-10 diagnoses M15 to M19) treated with acupuncture as the leading form of therapy were included in an observational study. Detailed questionnaires including instruments to measure pain intensity (numerical rating scales from 0 to 10), disability (Pain Disability Index) and quality of life (SF-36) were filled in before treatment, after treatment and at 6 months. Patients suffering from osteoarthritis of the knee and hip also filled in the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index questionnaire.

Results. A total of 736 patients were included in the main analysis. Seventy (10%) patients and 278 (38%) patients, respectively, suffered exclusively from primary osteoarthritis of the hip or knee, 239 (33%) from another type of osteoarthritis and 149 (20%) had more than one affected joint. On average, patients received 8.7 ± 3.1 acupuncture treatments. Statistically significant and clinically relevant improvements were seen in all subgroups both after treatment and at 6 months in all major outcome measures. In patients with osteoarthritis of the hip, the WOMAC sum score was 47.9 ± 20.7 at baseline, 34.8 ± 20.0 after treatment and 33.1 ± 22.2 at 6 months. The respective values in patients with osteoarthritis of the knee were 51.7 ± 20.9, 34.1 ± 23.3 and 34.6 ± 25.1.

Conclusions. In this study, patients with chronic pain due to osteoarthritis reported clinically relevant improvements after acupuncture treatment. Due to the uncontrolled design and the high proportion of patients lost to follow-up, the study findings must be interpreted cautiously.

Acupuncture, Complementary medicine, Osteoarthritis, Observational study

Acupuncture is one of the most widespread forms of complementary medicine. Surveys have shown that a relevant proportion of patients suffering from osteoarthritic pain seek acupuncture treatment [1–3]. A systematic review of randomized trials in patients suffering from osteoarthritis of the knee considered the available evidence as promising, but further, rigorous trials were considered necessary [4]. For arthritis of other joints, the evidence is even more scarce [5].

In Germany, treatment with acupuncture was often reimbursed by statutory sickness funds (which cover about 90% of the population) throughout the 1990s on an informal basis. Under increasing pressure to budget health-care costs, the German Federal Committee of Physicians and Statutory Sickness Funds decided in October 2000 that the scientific evidence supporting acupuncture was insufficient to justify routine reimbursement. However, it allowed the reimbursement of acupuncture treatment for a group of conditions where the evidence was considered promising (chronic osteoarthritic pain, chronic low back pain and chronic headaches) for a limited period, under the precondition that effectiveness was evaluated. Therefore, a group of statutory sickness funds initiated a research programme including both randomized trials and large-scale observational studies (the Programme for the Evaluation of Patient Care with Acupuncture; PEP-Ac) [6]. From this programme, we report here the results of an observational study in routine care in patients undergoing acupuncture treatment for osteoarthritic pain. Our objectives were to investigate (i) characteristics of patients with osteoarthritis undergoing acupuncture treatment; (ii) whether pain, function and quality of life change after treatment; and (iii) whether outcomes differ between patients with different types of osteoarthritis.

Patients and methods

Framework and setting

All patients with pain due to osteoarthritis, low back pain or headaches for more than 6 months and insured by a group of German statutory sickness funds covering about 20 million persons (about a quarter of the German population) have been able to receive acupuncture treatment since July 2001 under the preconditions that (i) the physician is accredited for the programme (major inclusion criteria: at least 140 h acupuncture training, license to provide medical care within the statutory sickness fund system); and (ii) at least basic information on characteristics, treatment and outcomes is documented by the physician. Patients have to pay €5 to €10 per session out of pocket depending on the acupuncture diploma held by the treating physician; approximately €25 per session is paid by the sickness funds. All patients are informed about the preconditions and procedures of the programme, and have to provide oral and written consent. The programme was approved by all relevant ethics boards (regional ethics committees of the German Medical Association). About half a million patients and about 10 000 physicians participated in the programme between August 2001 and July 2003. In 12.4% (61 099) of the patients osteoarthritic pain was reported as the primary diagnosis.

Patients

Physicians accredited for the programme were asked to participate in an observational study collecting more detailed information on a sample of patients. To avoid major selection effects and minimize workload, physicians were asked to screen the first six patients with headache, chronic low back pain or osteoarthritis born in a specific month allocated randomly to the physician by the study centre for inclusion in the observational study. General inclusion criteria were an age of at least 18 yr, knowledge of the German language, and ability to understand and fill in the questionnaires. Given the regulatory framework, patients with the following specific diagnoses could be included: polyarthritis (ICD-10 code M15); primary osteoarthritis of the hip (M16.0/1); dysplastic osteoarthritis of the hip (M16.2/3); post-traumatic osteoarthritis of the hip (M16.4/5); other secondary osteoarthritis of the hip (M16.6/7); primary osteoarthritis of the knee (M17.0/1); post-traumatic osteoarthritis of the knee (M17.2/3); other secondary osteoarthritis of the knee (M17.4/5); osteoarthritis of the thumb (M18); and primary, post-traumatic or other secondary osteoarthritis of other joints (M19.0/1/2). The diagnosis had to be confirmed by radiology, and the pain in the relevant joint had to have lasted at least 6 months. Patients with inflammatory polyarthritis or infectious arthropathy were excluded.

Interventions

Acupuncture (insertion of sterile disposable needles at classical acupuncture points) could be provided up to a maximum of 15 treatment sessions; however, after six and 10 sessions, physicians had to provide reasons to the sickness funds why further sessions were deemed necessary. Duration of sessions had to be at least 30 min. All other aspects of treatment were at the discretion of the treating physicians. Other treatments (medication, physiotherapy, etc.) could be prescribed as needed. Exclusive use of ear acupuncture, laser acupuncture or other non-classical techniques was not allowed.

Outcomes

Physicians were asked to document details of the patient's history and on the treatments performed and prescribed. Patients filled in a questionnaire before the first acupuncture session, after the last session, and 6 months after the first session. All handling of the questionnaires was at the discretion of the treating physician and the study centre only received anonymous data. The questionnaire was a modified version of the Pain Questionnaire of the German Society for the Study of Pain (DGSS). It included the following validated instruments: (i) the German version of the Pain Disability Index (PDI) [7]; (ii) a scale for assessing the sensory and affective aspects of pain (Schmerzempfindungs-Skala SES) [8]; (iii) the ADS depression scale (German version of the Center for Epidemiological Studies Depression Scale CES-D) [9]; and (iv) the German version of the Short Form 36 (SF-36) to assess health-related quality of life [10]. Furthermore, it included numerical rating scales for pain intensity and questions on patient characteristics as well as questions on the number of days with pain and pain killers during the last 4 weeks. We added questions on side-effects of acupuncture and a global assessment of perceived treatment efficacy. Patients suffering from osteoarthritis of the hip or knee were asked to fill in the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) questionnaire [11]. There was no single main outcome measure for confirmatory analysis, but predefined outcomes of major interest were the average pain during the last 4 weeks on a numerical rating scale, the Pain Disability Index, the physical component scale (physical health) from the SF-36 and the WOMAC sum score. An improvement of 50% compared with baseline values on the average pain rating or the Pain Disability Index was considered a clinically relevant response.

Analyses

For the analysis, patients were categorized into four diagnostic subgroups: (i) patients suffering exclusively from primary osteoarthritis of the hip (uni- or bilateral); (ii) patients suffering exclusively from primary osteoarthritis of the knee (uni- or bilateral); (iii) all patients with another single osteoarthritis diagnosis; and (iv) patients with osteoarthritis of two or more different joints. All data were analysed descriptively using SPSS software (version 11.5; SPSS, Chicago, IL, USA). We investigated differences between patients with complete data and missing follow-up data using Fisher's exact test, the χ² test, analysis of variance (ANOVA) and analysis of covariance (ANCOVA) (for metric outcomes adjusting for baseline values). Differences between all four diagnostic groups were compared using the χ² test and ANOVA. In addition, we did a comparison (t-test, χ² test and Fisher's exact test) restricted to the two most clearly defined groups of patients (with primary osteoarthritis of the hip and knee). ANCOVA was used to compare changes in clinical outcome measures after treatment and at 6 months with baseline values as covariates. Differences within groups were analysed using the t-test for paired samples. Due to the exploratory character of the analyses, we did not adjust for multiple testing.

Results

Patient selection

From a total of 1443 patients with osteoarthritic pain, 1167 met the inclusion criteria (see Fig. 1 for a flow chart). In 431 patients (37%), one or more questionnaires were missing. A total of 736 patients for whom all three questionnaires (at baseline, after treatment and at 6 months) were available, treated by 602 different physicians, were included in the main analysis. Patients providing all questionnaires did not differ significantly from those with missing questionnaires regarding age [mean (s.d.) 62.9 (12.5) vs 63.2 (12.8) yr; P = 0.628], sex (80 vs 77% female; P = 0.288), education (10 vs 14% longer than 10 yr; P = 0.064), disease duration (21 vs 21% longer than 10 yr, P = 0.937) and concomitant diseases (64 vs 64%, P = 0.899). The global assessment of efficacy of acupuncture was very similar among patients with a complete set of questionnaires and those for whom only the post-treatment questionnaire was available (20 vs 19% very good, 31 vs 31% good, 33 vs 33% moderate, 16 vs 18% insufficient; P = 0.966). Also, improvements regarding pain, disability, physical health and the WOMAC score did not differ substantially (P = 0.490, 0.183, 0.752 and 0.168 respectively).

Fig. 1.

Flow chart.

Patient characteristics

Seventy patients (10%) suffered exclusively from primary osteoarthritis of the hip and 278 (38%) exclusively from primary osteoarthritis of the knee (uni- or bilateral). For 239 (33%) patients, physicians coded another type of hip (18 patients) or knee arthritis (31 patients), or osteoarthritis of another joint (most often shoulder). One hundred and forty-nine (20%) patients were treated for arthritis of two or more different joints. Most frequent single diagnoses among these patients were polyarthritis (ICD-10 code M15, 95 patients), primary osteoarthritis of the knee (61 patients) and primary osteoarthritis of the hip (29 patients).

Patient characteristics and baseline values are presented in Tables 1 and 3. Patients were predominantly female (79.9%), reported an average pain level of 5.7 ± 1.9 (on a numerical rating scale ranging from 0 = no pain to 10 = worst imaginable pain) for the last 4 weeks, and suffered from relevant impairments in function and physical health; mental health was similar to that of a normal population. The mean number of doctor visits for pain in the previous 6 months ranged from 7.4 to 10.2 in the four diagnostic subgroups. Between 46 and 59% had had physiotherapy before inclusion in the study. Compared with patients with primary osteoarthritis of the knee, patients with primary osteoarthritis of the hip were less often female and had a less elevated body mass index. Baseline values for the main clinical outcome measures were similar. Differences became more apparent when all four groups were compared (Table 1, last column), with more complaints in patients having more than one affected joint.

Table 1.

Patient characteristics at baseline (mean and s.d. or percentage)

	Primary OA of the hip (n = 70)	Primary OA of the knee (n = 278)	Other (n = 239)	>1 joint (n = 149)	P-value (knee/hip)	P-value (all 4)
Female sex	73%	81%	77%	85%	0.140	0.116
Age	65.8 (10.9)	64.5 (11.5)	58.4 (13.2)	65.4 (12.1)	0.384	<0.001
Body mass index	26.1 (3.7)	28.1 (4.2)	26.1 (4.6)	26.9 (4.2)	0.001	<0.001
>10 yr school	12%	13%	13%	15%	0.926	0.345
Pain for >5 yr	30%	42%	28%	48%	0.099	<0.001
Pain intensity/disabilitya					0.326	0.077
Low/low	20%	26%	19%	14%
High/low	34%	30%	33%	29%
Moderate disability	33%	25%	28%	30%
Strong disability	13%	19%	21%	27%
Disability days for painb	67.4 (74.9)	75.1 (74.6)	73.4 (71.2)	88.6 (74.6)	0.439	0.134
Doctor visits for painb	8.1 (9.3)	7.9 (7.3)	7.4 (7.3)	10.2 (11.4)	0.896	0.021
Previous physiotherapyb	46%	46%	52%	59%	1.000	0.051
Mental health (SF-36)	50.7 (12.9)	50.6 (12.0)	47.7 (13.1)	47.0 (12.2)	0.977	0.012

The first P-value refers to the comparison of patients with osteoarthritis of the hip and knee; the second P-value refers to the comparison of all four groups. OA, osteoarthritis; ^bcategorization according to Von Korff et al. [17]; in the last 6 months; SF-36 = Short Form 36.

Table 2.

Additional treatments prescribed, provided or documented by physicians

	Primary OA of the hip (n = 70)	Primary OA of the knee (n = 278)	Other (n = 239)	>1 joint (n = 149)	All n = 736
Drugs (excluding acute pain treatment)	11%	10%	5%	17%	10%
Exercise	15%	12%	12%	15%	13%
Physiotherapy	27%	20%	20%	27%	22%
Other physical therapies	6%	4%	7%	7%	6%
Any of these	36%	32%	31%	38%	33%

Table 3.

Main outcome measures at baseline, after treatment and at 6 months

	Primary OA of the hip	Primary OA of the knee	Other	>1 joint	P-value (knee/hip)	P-value (all 4)
Average paina
Baseline	5.3 (1.7)	5.6 (1.9)	5.7 (1.8)	6.0 (2.1)	0.352	0.039
After treatment	3.8 (2.2)	3.7 (2.3)	3.6 (2.2)	4.1 (2.4)	0.510	0.147
6 months	3.4 (2.5)	3.6 (2.5)	3.2 (2.2)	4.0 (2.3)	0.706	0.017
Pain Disability Index (PDI)
Baseline	29.1 (15.2)	27.4 (13.8)	28.5 (14.1)	32.2 (15.6)	0.403	0.022
After treatment	20.8 (13.3)	18.6 (14.3)	19.0 (15.1)	22.3 (15.8)	0.368	0.668
6 months	18.6 (14.8)	17.7 (15.7)	16.3 (14.8)	23.2 (16.6)	0.611	0.025
Physical health (SF-36)b
Baseline	29.0 (8.2)	28.4 (8.0)	31.7 (7.6)	27.7 (8.0)	0.559	<0.001
After treatment	34.8 (8.4)	34.6 (9.8)	37.9 (9.8)	33.4 (9.8)	0.459	0.364
6 months	35.8 (10.2)	35.9 (10.4)	39.3 (11.1)	33.4 (10.4)	0.710	0.033
WOMAC total score
Baseline	47.9 (20.7)	51.7 (20.9)			0.215	n.a.
After treatment	34.8 (20.0)	34.1 (23.3)			0.252	n.a.
6 months	33.1 (22.2)	34.6 (25.1)			0.826	n.a.
Global assessment effectc					0.222	0.071
Very good	15%	17%	23%	13%
Good	38%	25%	29%	21%
Moderate	24%	35%	27%	34%
Little	14%	16%	14%	21%
None	9%	8%	7%	11%

Values are mean and s.d. P-values for baseline comparisons are derived from ANOVA. P-values for comparisons after treatment and at 6 months are derived from ANCOVA adjusting for baseline differences between diagnostic subgroups. All changes compared with baseline are statistically highly significant (P<0.001, ANOVA). ^aWithin the last 4 weeks; ^bhigher values indicate better status; ^cafter 6 months. n.a. not applicable; For abbreviations see footnote of Table 1.

Treatment

The mean number of acupuncture sessions was 8.7 ± 3.1 and was similar in all four diagnostic groups. The median duration of the treatment cycle was 43 days. On average, patients took acute pain medication on 11.3 ± 11.2 days in the 4 weeks preceding acupuncture treatment, and on 6.9 ± 10.7 days during the last 4 weeks of acupuncture treatment. In 33% of patients, physicians prescribed or provided physiotherapy, exercise, drug treatment (other than for acute pain on an as needed basis) or other physical therapies (Table 2).

Treatment outcomes

After treatment and 6 months after inclusion, patients reported less pain, medication use and disability, better physical health (Table 3), mental health, better scores for sensory and affective aspects of pain, and lower depression scores. All changes were statistically highly significant (P<0.001) in all subgroups except for mental health in patients with hip osteoarthritis. Average pain in patients with osteoarthritis of the hip decreased from 5.3 at baseline to 3.8 after treatment and 3.4 at 6 months. The respective values were 5.6, 3.7 and 3.6 in patients with osteoarthritis of the hip; 5.7, 3.6 and 3.2 in patients with other osteoarthritis; and 6.0, 4.1 and 4.0 in patients with more than one affected joint. After treatment the Pain Disability Index had decreased by 50% or more compared with baseline in 34% of patients, at 6 months this figure rose to 43%; for average pain the figures were 38 and 44%, respectively. In patients with primary hip or knee osteoarthritis, WOMAC subscores and the sum scores decreased significantly (Fig. 2). Changes were very similar in patients with knee and hip osteoarthritis. Follow-up results tended to be best in patients with other osteoarthritis while patients with more than one affected joint had the least favourable results. There were no significant differences between patients receiving additional treatment and those who only received acupuncture. After 6 months 18% of patients assessed the therapeutic effect of acupuncture as very good, 27% as good, 31% as moderate, 16% as little and 8% no benefit at all. Side-effects were reported by 51 patients (7% of the 724 answering the question). The most frequent side-effects were fatigue, haematoma and pain. Eleven patients considered their side-effects as truly bothersome; all others considered the side-effects as minor or very minor.

Fig. 2.

WOMAC subscores pain, stiffness and function at baseline, after acupuncture treatment and at 6 months in patients suffering exclusively from primary osteoarthritis (OA) of the hip or knee. Values are means and 95% confidence intervals. All changes from baseline are statistically highly significant (P<0.001).

Sensitivity analyses

To investigate the possible impact of the large loss to follow-up, we performed two sensitivity analyses including all 1167 patients included in the study. If missing values were replaced according to the last-value carried forward approach, the effect size decreased only moderately. The improvement in the Pain Disability Index decreased by 14% (from 8.8 score points to 7.6 score points, all subgroups pooled) after treatment and by 16% (from 10.1 to 8.5) after 6 months. For the pain rating (numerical rating scale from 0 to 10), the figures were 7% (from 1.9 to 1.8) after treatment and 6% (from 2.1 to 2.0) at follow-up. Given the large number of patients with post-treatment data not providing the follow-up questionnaire, the decrease at 6 months was much larger if missing values were replaced by baseline values: 41% (from 10.1 to 5.9) for the Pain Disability Index and 37% (from 2.1 to 1.3) for the pain rating. Changes from baseline are still statistically highly significant with both replacement methods.

Discussion

Principal findings

The results of this pragmatic, uncontrolled, observational study, show that under current regulatory conditions in Germany physicians treat patients with a variety of osteoarthritic conditions, with acupuncture as the leading form of therapy. Osteoarthritis of the knee is the most frequently treated single condition. In all subgroups, patients providing sufficient data reported clinically relevant improvements which lasted up to 6 months.

Strength and weaknesses

It has to be emphasized that our study cannot be compared to a clinical trial in which an experimental intervention is investigated under controlled conditions in a well-defined selection of patients. Instead, our study aimed to document to whom, how and with what outcome acupuncture is provided in routine practice under current regulations in Germany. Such a pragmatic approach has advantages and drawbacks. Clear strengths of our study are the large sample size and its external validity. The large sample size warrants sufficient power when comparing the diagnostic subgroups. The minimal interference of the study with routine practice makes it likely that the findings reflect current practice in Germany. The questionnaire used is recommended by the German Society for the Study of Pain for documentation in patients with chronic pain and is widely applied in Germany [12]. The variety of instruments included in the questionnaire made it possible to collect data on different aspects of pain and direct comparisons with other pain conditions (chronic low back pain, headache) treated with acupuncture within the same programme.

An important shortcoming of our study is the low follow-up rate. As the coordinating research centre did not have access to names and addresses of patients, the local organization of the study was completely in the hands of the physicians (who did not receive any additional financial incentive for participating in the observational study). Our comparison of patients with complete and incomplete data as well as the communication with physicians during the study suggest that a relevant part of the loss to follow-up is due to organizational problems and not related to treatment failure. Still, it is likely that some of the loss was due to dissatisfaction of patients and that particularly the follow-up results are to some extent overoptimistic. It is also impossible to rule out that some patients answered questionnaires in an overoptimistic manner to please their doctors. Hence, the size of improvements reported must be interpreted with great caution. However, the results of our sensitivity analysis in which all missing data were replaced by baseline values is likely to be over-conservative. Furthermore, it seems unlikely that selection bias and effects of co-interventions should differ strongly between the diagnostic subgroups. Therefore, the comparison between these subgroups should provide valid data.

Another shortcoming from a scientific point of view is the diagnostic heterogeneity in our study. Particularly, in the subgroup ‘other osteoarthritis’, a number of patients might have been coded incorrectly. However, as it was our explicit objective to monitor routine practice as closely as possible, this problem seems inevitable.

Interpretation of findings

It is not possible to draw causal inferences from our study on the effectiveness of acupuncture as it did not include a control group. The relative impact of placebo effects, unspecific needling effects and concomitant treatments on the observed outcomes remains unclear. Therefore, we performed in parallel a randomized controlled trial comparing acupuncture with minimal acupuncture (superficial needling of non-acupuncture points) and a waiting list control in patients with osteoarthritis of the knee [13]. In this trial, acupuncture was significantly superior to both minimal acupuncture and waiting list control after 8 weeks. After 6 and 12 months, differences between acupuncture and minimal acupuncture were no longer significant. Absolute improvement in the WOMAC index was slightly higher than that observed in the observational study. Changes for the pain disability index and physical health were very similar in the two studies.

Our results are in accordance with the promising results from randomized trials on acupuncture for osteoarthritis of the knee reviewed by Ezzo et al. [4] as well as a recently published large randomized trial by Berman et al. [14]. Overall, the available evidence suggests that acupuncture is effective in the treatment of osteoarthritis of the knee. However, a relevant part of the effect might be due to unspecific needling effects or placebo effects. Due to the lack of studies, it is difficult to compare our results with those of studies of other types of osteoarthritis.

All parts of the research project show that a majority of patients seeking acupuncture treatment were women. This was probably due to two factors. First, about 60% of the persons insured by the participating statutory sickness funds are female. Second, surveys have shown repeatedly that women are more likely to use complementary therapies than men [15, 16].

While chronic low back pain and headaches were more prevalent within the reimbursement programme, chronic pain due to osteoarthritis was an important indication, with about 60 000 patients (in a total population of about 20 million insured subjects) treated within a period of 2 yr. The results of our studies suggest that patients experience clinically relevant improvement after a treatment cycle with acupuncture. Side-effects were infrequent and minor, and the amount of pain medication consumed by patients decreased considerably. As acupuncture is a time-intensive intervention, economic analyses are desirable to assess its cost-effectiveness.

It is not fully clear whether the findings from this study are valid for other countries. Only physicians with a minimum of training in acupuncture were allowed to participate. In other countries, acupuncture is often practised by non-medical persons who, however, tend to have much longer training. Physicians in Germany practice a comparably traditional style (based on the principles of Chinese medicine) of acupuncture while physicians in the UK often apply a more Western style. Furthermore, the specific reimbursement situation and the generally positive attitude of German patients towards acupuncture might limit the generalizability of our findings.

Conclusions

In conclusion, our study found that, under conditions of routine care in Germany, patients with osteoarthritic pain report a clinically relevant benefit from acupuncture. As our study did not include a control group and some of the patients received concomitant treatments, it is unclear whether the improvements observed are caused by the acupuncture intervention. Due the high proportion of patients lost to follow-up, the size of improvements after 6 months must be interpreted with great caution. Still, the findings of this observational study suggest that the positive effects of acupuncture observed in randomized trials in patients with osteoarthritis of the knee can also be obtained under conditions of routine practice, at least under the current regulation in Germany. Therefore, acupuncture seems to be a viable treatment option for the treatment of osteoarthritic pain.

The research programme on acupuncture is funded by the following German statutory sickness funds: Deutsche Angestellten-Krankenkasse (DAK), Hamburg; Barmer Ersatzkasse (BEK), Wuppertal; Kaufmännische Krankenkasse (KKH), Hannover; Hamburg-Münchener Krankenkasse (HaMü), Hamburg; Hanseatische Krankenkasse (HEK), Hamburg; Gmünder Ersatzkasse (GEK), Schwäbisch Gmünd; HZK Krankenkasse für Bau- und Holzberufe, Hamburg; Brühler Ersatzkasse, Solingen; Krankenkasse Eintracht Heusenstamm (KEH), Heusenstamm; Buchdrucker Krankenkasse (BK), Hannover.

The authors have declared no conflicts of interest.

Author notes

1Centre for Complementary Medicine Research, Department of Internal Medicine II, Technische Universität München, Kaiserstrasse 9, 80801 Munich, Germany and 2Division of Complementary Medicine, Department of Internal Medicine, University Hospital, Zurich, Switzerland.