Correction to: Complementary and alternative medicine for treatment of atopic eczema in children under 14 years old: a systematic review and meta-analysis of randomized controlled trials.

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Which risk understandings can be derived from the current disharmonized regulation of complementary and alternative medicine in Europe?

BACKGROUND: Many European citizens are seeking complementary and alternative medicine (CAM). These treatments are regulated very differently in the EU/EFTA countries. This may demonstrate differences in how risk associated with the use of CAM is perceived. Since most CAM treatments are practiced fairly similarly across Europe, differing risk understandings may influence patient safety for European CAM users. The overall aim of this article is thus to contribute to an overview and awareness of possible differing risk understandings in the field of CAM at a policymaking/structural level in Europe. METHODS: The study is a re-analysis of data collected in the CAMbrella EU FP7 document and interview study on the regulation of CAM in 39 European countries. The 12 CAM modalities included in the CAMbrella study were ranked with regard to assumed risk potential depending on the number of countries limiting its practice to regulated professions. The 39 countries were ranked according to how many of the included CAM modalities they limit to be practiced by regulated professions. RESULTS: Twelve of 39 countries generally understand the included CAM treatments to represent "high risk", 20 countries "low risk", while the remaining 7 countries understand CAM treatments as carrying "very little or no risk". The CAM modalities seen as carrying a risk high enough to warrant professional regulation in the highest number of countries are chiropractic, acupuncture, massage, homeopathy and osteopathy. The countries understanding most of the CAM modalities in the study as potentially high-risk treatments are with two exceptions (Portugal and Belgium) all concentrated in the southeastern region of Europe. CONCLUSION: The variation in regulation of CAM may represent a substantial lack of common risk understandings between health policymakers in Europe. We think the discrepancies in regulation are to a considerable degree also based on factors unrelated to patient risk. We argue that it is important for patient safety that policy makers across Europe address this confusing situation. This could be done by applying the WHO patient safety definitions and EU's policy to facilitate access to "safe and high-quality healthcare", and regulate CAM accordingly.

Prevalence and reasons for intentional use of complementary and alternative medicine as an adjunct to future visits to a medical doctor for chronic disease.

BACKGROUND: Intentional use of complementary and alternative medicine (CAM) has previously only been researched in small, possibly biased, samples. There seems to be a lack of scientific information regarding healthy individual's attitudes and presumed use of CAM. The aim of this study is to describe prevalence and characteristics of participants who intend to see a CAM provider compared to participants who intend to see a medical doctor (MD) only when suffering from a chronic, non- life-threatening disease and in the need of treatment. Further to describe differences between the groups regarding expected reasons for CAM use and expected skills of CAM providers. METHOD: The survey was conducted in January 2016 as part of the "TNS Gallup Health policy Barometer". In total, 1728 individuals aged 16-92 years participated in the study, constituting an overall response rate of 47%. The survey included questions regarding opinions and attitudes towards health, health services and health politics in Norway. RESULTS: The majority of the participants (90.2%) would see a MD only if they were suffering from a chronic, non- life-threatening disease and were in the need of treatment. Men over the age of 60 with a university education tended to see a MD only. Only 9.8% of all respondents would in addition visit a CAM provider. Being an intentional user of a MD + CAM provider was associated with being a woman under the age of 60. The respondents believed that CAM providers have professional competence based on formal training in CAM. They also believed that individuals seeing a CAM provider have poor health and are driven by the hope of being cured. Further, that they have heard that others have good experience with such treatment. CONCLUSION: Intentional use of CAM is associated with positive attitudes, trustworthiness, and presumed positive experiences in the CAM-patient-setting. Intentional CAM users also have the impression that CAM providers have professional competence based on formal training in alternative therapies.

Complementary and alternative medicine for treatment of atopic eczema in children under 14 years old: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Due to limitations of conventional medicine for atopic eczema (AE), complementary and alternative medicine (CAM) is widely used as an alternative, maintaining, or simultaneous treatment for AE. We aimed to evaluate the beneficial and harmful effects of CAM for children with AE under 14 years old. METHODS: We searched for randomized trials on CAM in 12 Chinese and English databases from their inception to May 2018. We included children (< 14 years) diagnosed with AE, who received CAM therapy alone or combined with conventional medicine. We extracted data, and used the Cochrane "Risk of bias" tool to assess methodological quality. Effect was presented as relative risk (RR) or mean difference (MD) with 95% confidence interval (CI) using RevMan 5.3. RESULTS: Twenty-four randomized controlled trials involving 2233 children with AE were included. Methodological quality was of unclear or high risk of bias in general. The trials tested 5 different types of CAM therapies, including probiotics, diet, biofilm, borage oil, and swimming. Compared to placebo, probiotics showed improved effect for the SCORAD index (MD 9.01, 95% CI 7.12-10.90; n = 5). For symptoms and signs such as itching, skin lesions, CAM combined with usual care was more effective for symptom relief ≥95% (RR 1.47, 95% CI 1.30-1.68; n = 8), and for ≥50% symptoms improvement (RR 1.34, 1.25-1.45; n = 9) compared to usual care. There was no statistic significant difference between CAM and usual care on ≥95% improvement or ≥ 50% improvement of symptoms. However, swimming, diet and biofilm showed improvement of clinical symptoms compared with usual care. At follow-up of 8 weeks to 3 years, CAM alone or combined with usual care showed lower relapse rate (RR 0.38, 0.28-0.51, n = 2; RR 0.31, 0.24-0.40, n = 7; respectively) compared to usual care. Twelve out of 24 trials reported no occurrence of severe adverse events. CONCLUSIONS: Low evidence demonstrates that some CAM modalities may improve symptoms of childhood AE and reduce relapse rate. Safety remains unclear due to insufficient reporting. Further well-designed randomized trials are needed to confirm the potential beneficial effect and to establish safety use.

High prevalence but limited evidence in complementary and alternative medicine: guidelines for future research.

The use of complementary and alternative Medicine (CAM) has increased over the past two decades in Europe. Nonetheless, research investigating the evidence to support its use remains limited. The CAMbrella project funded by the European Commission aimed to develop a strategic research agenda starting by systematically evaluating the state of CAM in the EU. CAMbrella involved 9 work packages covering issues such as the definition of CAM; its legal status, provision and use in the EU; and a synthesis of international research perspectives. Based on the work package reports, we developed a strategic and methodologically robust research roadmap based on expert workshops, a systematic Delphi-based process and a final consensus conference. The CAMbrella project suggests six core areas for research to examine the potential contribution of CAM to the health care challenges faced by the EU. These areas include evaluating the prevalence of CAM use in Europe; the EU cititzens' needs and attitudes regarding CAM; the safety of CAM; the comparative effectiveness of CAM; the effects of meaning and context on CAM outcomes; and different models for integrating CAM into existing health care systems. CAM research should use methods generally accepted in the evaluation of health services, including comparative effectiveness studies and mixed-methods designs. A research strategy is urgently needed, ideally led by a European CAM coordinating research office dedicated to fostering systematic communication between EU governments, the public, charitable and industry funders, researchers and other stakeholders. A European Centre for CAM should also be established to monitor and further a coordinated research strategy with sufficient funds to commission and promote high quality, independent research focusing on the public's health needs and pan-European collaboration. There is a disparity between highly prevalent use of CAM in Europe and solid knowledge about it. A strategic approach on CAM research should be established to investigate the identified gaps of knowledge and to address upcoming health care challenges.

Serum level of under-carboxylated osteocalcin and bone mineral density in early menopausal Norwegian women.

PURPOSE: Serum level of under-carboxylated osteocalcin (ucOC) is considered a sensitive measure of vitamin K status, and ucOC levels are associated with bone mineral density (BMD) and fracture risk in elderly persons. The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women. METHODS: The data reported here come from the enrollment in a double-blinded placebo-controlled randomized trial comprising 334 healthy Norwegian women between 50 and 60 years, 1-5 years after menopause, not using warfarin or medication known to affect bone metabolism. Total hip, femoral neck, lumbar spine, and total body BMD and serum level of ucOC and total osteocalcin were measured, and information of lifestyle was collected through questionnaires. The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables. RESULTS: The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites, both in univariate analyses (p < 0.01) and in multivariate analyses adjusting for years since menopause, smoking status and weight (p < 0.01). However, serum ucOC, expressed as percentage of the total osteocalcin level, was not associated with BMD at any site. CONCLUSIONS: Achievement of adequate vitamin K nutritional intake is important, but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women.

Reflexology for acute rhinosinusitis - Results from a blinded, early-phase comparative trial.

BACKGROUND: Reflexology is commonly used as an adjunct to conventional treatment by patients with respiratory tract infections. The effect of reflexology needs to be tested in a full-scale randomized controlled study. Small early-phase trials can give an indication on whether full-size clinical trials are warranted. The objective of this study is to determine whether the study design is feasible in a full-scale study of reflexology as an add-on to usual care compared to usual care alone in acute rhinosinusitis, and further if there is a statistical indication of an effect of reflexology warranting a full-scale study. METHODS: 20 patients with symptoms compatible with acute rhinosinusitis, and an illness duration of 28 days or less were randomized to additional reflexology treatment along with usual medical care, or usual care alone. The patients scored how much each of 16 sinus-related symptoms bothered them in the past few days on a six-point scale (zero = no problem to five = severe problem). To determine if there is a statistical indication of an effect of reflexology warranting a full-scale study, the separation test was used. RESULTS: The methodology was considered feasible and could therefore be applied in a full-scale study of reflexology for acute rhinosinusitis. The mean reduction in symptom score from baseline to day two was 0.95 in the reflexology group and 0.78 in the control group. From baseline to day ten the mean reduction in symptom score was 2.12 in the reflexology group and 1.63 in the control group. A statistical indication of effect in a full-scale study in favor of reflexology was found from baseline to day ten but not from baseline to day two. CONCLUSIONS: The research methodology in this study could be used in a full-scale study of reflexology in acute sinusitis. The results from the separation test indicates an effect warranting a full-scale study of reflexology regarding effects in acute sinusitis ten days after treatment.

Any difference? Use of a CAM provider among cancer patients, coronary heart disease (CHD) patients and individuals with no cancer/CHD.

BACKGROUND: Although use of complementary and alternative medicine (CAM) among cancer patients has been described previously, prevalence of use has not commonly been compared to other disease groups in a true population sample where CAM use or cancer is not the main focus. The aims of the present study are to (1) examine how CAM use in cancer patients differs from people with a previous CHD diagnosis and people with no cancer or CHD diagnosis in an unselected general population and (2), investigate the use of a CAM provider among individuals with a previous cancer diagnosis. METHODS: A total of 8040 men and women aged 29 to 87 in the city of Tromsø, Norway filled in a questionnaire developed specifically for the Tromsø V study with questions on life style and health issues. Visits to a CAM provider within the last 12 months and information on cancer, heart attack and angina pectoris (heart cramp) were among the questions. 1449 respondents were excluded from the analyses. RESULTS: Among the 6591 analysed respondents 331 had a prior cancer diagnosis, of whom 7.9% reported to have seen a CAM provider within the last 12 months. This did not differ significantly from neither the CHD group (6.4%, p = 0.402) nor the no cancer/CHD group (9.5%, p = 0.325). CONCLUSION: According to this study, the proportion of cancer patients seeing a CAM provider was not statistically significantly different from patients with CHD or individuals without cancer or CHD.

Use of complementary and alternative medicine at Norwegian and Danish hospitals.

BACKGROUND: Several studies have found that a high proportion of the population in western countries use complementary and alternative medicine (CAM). However, little is known about whether CAM is offered in hospitals. The aim of this study was to describe to what extent CAM is offered in Norwegian and Danish hospitals and investigate possible changes in Norway since 2001. METHODS: A one-page questionnaire was sent to all included hospitals in both countries. The questionnaire was sent to the person responsible for the clinical activity, typically the medical director. 99 hospitals in the authority (85%) in Norway and 126 in Denmark (97%) responded. Given contact persons were interviewed. RESULTS: CAM is presently offered in about 50% of Norwegian hospitals and one-third of Danish hospitals. In Norway CAM was offered in 50 hospitals, 40 of which involved acupuncture. 19 hospitals gave other alternative therapies like biofeedback, hypnosis, cupping, ear-acupuncture, herbal medicine, art therapy, homeopathy, reflexology, thought field therapy, gestalt therapy, aromatherapy, tai chi, acupressure, yoga, pilates and other. 9 hospitals offered more than one therapy form. In Denmark 38 hospitals offered acupuncture and one Eye Movement Desensitization and Reprocessing Light Therapy. The most commonly reported reason for offering CAM was scientific evidence in Denmark. In Norway it was the interest of a hospital employee, except for acupuncture where the introduction is more often initiated by the leadership and is more based on scientific evidence of effect. All persons (except one) responsible for the alternative treatment had a medical or allied health professional background and their education/training in CAM treatment varied substantially. CONCLUSIONS: The extent of CAM being offered has increased substantially in Norway during the first decade of the 21(st) century. This might indicate a shift in attitude regarding CAM within the conventional health care system.

A prospective study of sex steroids, sex hormone-binding globulin, and non-vertebral fractures in women and men: the Tromso Study.

OBJECTIVES: As bone fragility is partly the result of sex hormone deficiency, we sought to determine whether circulating sex steroids or sex hormone-binding globulin (SHBG) predicts non-vertebral fractures. METHODS: Forearm bone mineral density (BMD), total estradiol and testosterone, calculated free levels, and SHBG were measured in 1386 postmenopausal women and 1364 men aged 50-84 years at baseline in the Tromsø Study (1994-1995). Non-vertebral fractures were documented between 1994 and 2005. RESULTS: During 8.4 years (range 0.01-10.4) of follow-up, 281 women and 105 men suffered non-vertebral fractures. For both sexes, fracture cases had lower BMD and higher SHBG, but sex steroids were not lower. Each standard deviation (s.d.) increase in SHBG increased non-vertebral fracture risk in women (hazards ratio (HR) 1.17; 95% confidence interval (CI) 1.03-1.33) and men (HR 1.26; 95% CI 1.03-1.54). After further adjustment for BMD, the risk was not statistically significant in women (HR 1.09; 95% CI 0.95-1.24) or men (HR 1.22; 95% CI 0.99-1.49). Each s.d. decrease in BMD increased fracture risk in women (HR 1.36; 95% CI 1.19-1.56) and men (HR 1.41; 95% CI 1.15-1.73). Fracture rates were highest in participants with SHBG in the highest tertile and BMD in the lowest tertile and were 37.9 and 17.0 per 1000 person-years in women and men respectively. However, in both sexes the combination of BMD and SHBG was no better predictor of fracture risk than BMD alone. Sex steroids were not associated with fracture risk. CONCLUSIONS: Measurements of sex steroids or SHBG are unlikely to assist in decision making regarding fracture risk susceptibility.

Researching complementary and alternative treatments--the gatekeepers are not at home.

BACKGROUND: To explore the strengths and weaknesses of conventional biomedical research strategies and methods as applied to complementary and alternative medicine (CAM), and to suggest a new research framework for assessing these treatment modalities. DISCUSSION: There appears to be a gap between published studies showing little or no efficacy of CAM, and reports of substantial clinical benefit from patients and CAM practitioners. This "gap" might be partially due to the current focus on placebo-controlled randomized trials, which are appropriately designed to answer questions about the efficacy and safety of pharmaceutical agents. In an attempt to fit this assessment strategy, complex CAM treatment approaches have been dissected into standardized and often simplified treatment methods, and outcomes have been limited. Unlike conventional medicine, CAM has no regulatory or financial gatekeeper controlling their therapeutic "agents" before they are marketed. Treatments may thus be in widespread use before researchers know of their existence. In addition, the treatments are often provided as an integrated 'whole system' of care, without careful consideration of the safety issue. We propose a five-phase strategy for assessing CAM built on the acknowledgement of the inherent, unique aspects of CAM treatments and their regulatory status in most Western countries. These phases comprise: 1. Context, paradigms, philosophical understanding and utilization 2. Safety status 3. Comparative effectiveness. 4. Component efficacy 5. Biological mechanisms. SUMMARY: Using the proposed strategy will generate evidence relevant to clinical practice, while acknowledging the absence of regulatory and financial gatekeepers for CAM. It will also emphasize the important but subtle differences between CAM and conventional medical practice.

The effect of TCM acupuncture on hot flushes among menopausal women (ACUFLASH) study: a study protocol of an ongoing multi-centre randomised controlled clinical trial.

BACKGROUND: After menopause, 10-20% of all women have nearly intolerable hot flushes. Long term use of hormone replacement therapy involves a health risk, and many women seek alternative strategies to relieve climacteric complaints. Acupuncture is one of the most frequently used complementary therapies in Norway. We designed a study to evaluate whether Traditional Chinese Medicine acupuncture-care together with self-care is more effective than self-care alone to relieve climacteric complaints. METHODS/DESIGN: The study is a multi-centre pragmatic randomised controlled trial with two parallel arms. Participants are postmenopausal women who document > or =7 flushes/24 hours and who are not using hormone replacement therapy or other medication that may influence flushes. According to power calculations 200 women are needed to detect a 50% reduction in flushes, and altogether 286 women will be recruited to allow for a 30% dropout rate. The treatment group receives 10 sessions of Traditional Chinese Medicine acupuncture-care and self-care; the control group will engage in self-care only. A team of experienced Traditional Chinese Medicine acupuncturists give acupuncture treatments. DISCUSSION: The study tests acupuncture as a complete treatment package including the therapeutic relationship and expectation. The intervention period lasts for 12 weeks, with follow up at 6 and 12 months. Primary endpoint is change in daily hot flush frequency in the two groups from baseline to 12 weeks; secondary endpoint is health related quality of life, assessed by the Women's Health Questionnaire. We also collect data on Traditional Chinese Medicine diagnoses, and we examine treatment experiences using a qualitative approach. Finally we measure biological variables, to examine potential mechanisms for the effect of acupuncture. The study is funded by The Research Council of Norway.

NHS letter stimulates international dialogue on interpretation and possible implications of CAM research.

Prompted by the open letter by 13 prominent British scientists to National Health Science (NHS) trusts questioning the use of homeopathy, Vinjar Fønnebø, M.D., Ph.D., and Michael Baum, M.B., Ch.M., F.R.C.S., M.D.(Hon) entered into an e-mail exchange about the issues of research and documentation of practices in "complementary," "alternative," and "integrated" medicine. The paper presents the whole exchange unedited. Researchers who are well-acquainted with the field benefit from discussing and challenging, and will achieve a clearer understanding of both the understanding and opinions of the others as well as their own positions.

Presence of minor and major mental health impairment in adolescence and death from suicide and unintentional injuries/accidents in men: a national longitudinal cohort study.

OBJECTIVE: To examine the association between minor and major mental health impairment in late adolescence and death from suicide and unintentional injuries/accidents in men. METHODS: In Norway, all men attend a compulsory military medical and psychological examination. We included 558 949 men aged 17-19 years at the time of military examination in 1980-1999 and followed them up for death from suicide and unintentional injuries/accidents until the end of 2013. We used Cox proportional hazard models to examine the association between the presence of minor and major mental health impairments at examination and death from suicide and unintentional injuries/accidents. RESULTS: Compared to men with no mental health impairment, those with minor mental health impairment was associated with an increased risk of death from suicide (adjusted HR (HRadj)=1.63, 95% CI 1.39 to 1.92), transport accidents (HRadj=1.33, 95% CI 1.09 to 1.63), accidental poisoning (HRadj=2.27, 95% CI 1.79 to 2.88) and other unintentional injuries/accidents (HRadj=1.54, 95% CI 1.17 to 2.02). In men with major mental health impairment, the risk of death from suicide and accidental poisoning was elevated two times (HRadj=2.29, 95% CI 1.85 to 2.85) and three times (HRadj=3.53, 95% CI 2.61 to 4.79), respectively. CONCLUSIONS: We found an increased risk of death from suicide and unintentional injuries/accidents in men who had minor and major mental health impairment at age 17-19 years.

Circular instead of hierarchical: methodological principles for the evaluation of complex interventions.

BACKGROUND: The reasoning behind evaluating medical interventions is that a hierarchy of methods exists which successively produce improved and therefore more rigorous evidence based medicine upon which to make clinical decisions. At the foundation of this hierarchy are case studies, retrospective and prospective case series, followed by cohort studies with historical and concomitant non-randomized controls. Open-label randomized controlled studies (RCTs), and finally blinded, placebo-controlled RCTs, which offer most internal validity are considered the most reliable evidence. Rigorous RCTs remove bias. Evidence from RCTs forms the basis of meta-analyses and systematic reviews. This hierarchy, founded on a pharmacological model of therapy, is generalized to other interventions which may be complex and non-pharmacological (healing, acupuncture and surgery). DISCUSSION: The hierarchical model is valid for limited questions of efficacy, for instance for regulatory purposes and newly devised products and pharmacological preparations. It is inadequate for the evaluation of complex interventions such as physiotherapy, surgery and complementary and alternative medicine (CAM). This has to do with the essential tension between internal validity (rigor and the removal of bias) and external validity (generalizability). SUMMARY: Instead of an Evidence Hierarchy, we propose a Circular Model. This would imply a multiplicity of methods, using different designs, counterbalancing their individual strengths and weaknesses to arrive at pragmatic but equally rigorous evidence which would provide significant assistance in clinical and health systems innovation. Such evidence would better inform national health care technology assessment agencies and promote evidence based health reform.