What do Cochrane systematic reviews say about new practices on integrative medicine?

ABSTRACT BACKGROUND: This study identified and summarized all Cochrane systematic reviews (SRs) on the effects of ten integrative practices that were recently added to the Brazilian public healthcare system (SUS). DESIGN AND SETTING: Review of systematic reviews, conducted in the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (Unifesp). METHODS: Review of Cochrane SRs on the following interventions were identified, summarized and critically assessed: apitherapy, aromatherapy, bioenergetics, family constellation, flower therapy, chromotherapy, geotherapy, hypnotherapy, hand imposition or ozone therapy. RESULTS: We included a total of 16 SRs: 4 on apitherapy, 4 on aromatherapy, 6 on hypnotherapy and 2 on ozone therapy. No Cochrane SR was found regarding bioenergetics, family constellation, chromotherapy, clay therapy, flower therapy or hand imposition. The only high-quality evidence was in relation to the potential benefit of apitherapy, specifically regarding some benefits from honey dressings for partial healing of burn wounds, for reduction of coughing among children with acute coughs and for preventing allergic reactions to insect stings. CONCLUSION: Except for some specific uses of apitherapy (honey for burn wounds and for acute coughs and bee venom for allergic reactions to insect stings), the use of ten integrative practices that have recently been incorporated into SUS does not seem to be supported by evidence from Cochrane SRs.


INTRODUCTION
On March 2018, the Brazilian Ministry of Health announced an expansion of its policies for integrative practices for healthcare within the Brazilian public healthcare system (Sistema Único de Saúde, SUS). Thus, ten new types of integrative practices now form part of the list of procedures available through SUS: apitherapy, aromatherapy, bioenergetics, family constellation, chromotherapy, clay therapy, hypnotherapy, hand imposition, ozone therapy and flower therapy. 1 The term "integrative practice" commonly refers to incorporation of complementary approaches into a healthcare system. 2 It is important to differentiate between the concepts of "alternative" and "complementary" practices. When a non-mainstream practice is used together with conventional medicine, it is considered to be "complementary. " Conversely, when a non-mainstream practice is used in place of conventional medicine, it is considered to be "alternative. " Purely alternative approaches are seen less frequently, given that most people using non-mainstream approaches do so alongside conventional approaches. 2 Most complementary healthcare practices can be classified as use of natural products or as use of mind and body practices. They may include use of probiotics, dietary supplements, yoga, chiropractic and osteopathic manipulation, meditation, massage therapy, acupuncture, healing touch, hypnotherapy, etc. 2 Use of integrative practices may be justified for patients with chronic non-transmissible conditions whose clinical manifestations remain resistant or unresponsive to conventional treatments. However, their effectiveness and safety, and subsequently their cost-effectiveness and budgetary impact, need to be evaluated in order to guide their incorporation into public or private healthcare systems.
In this review, we identified and summarized all the Cochrane systematic reviews on the benefits and harm from use of ten integrative approaches that have recently been made available for users of SUS.

OBJECTIVE
To summarize the evidence from Cochrane systematic reviews focusing on ten integrative practices for preventive or therapeutic purposes, for any disease or condition.

Design
Review of Cochrane systematic reviews.

Discipline of Evidence-Based Medicine of Escola Paulista de Medicina (EPM), Universidade
Federal de São Paulo (UNIFESP), and Cochrane Brazil.

Types of studies
We considered the latest version of full Cochrane systematic reviews (SR). We excluded any protocol or any SR marked as "withdrawn" in the Cochrane Database of Systematic Reviews (CDSR).

Types of participants
We considered any healthy participant who received integrative practices for preventive purposes and any participant presenting any condition of illness who received integrative practices for therapeutic purposes.

Types of interventions
We included the integrative practices listed below that were used for preventive or therapeutic purposes and compared their use with no intervention or use of placebo or any other pharmacological or non-pharmacological intervention that was considered to represent a conventional, alternative or complementary approach. The integrative practices considered in this review are the same that are now provided in the Brazilian public health system, and comprised: apitherapy, aromatherapy, bioenergetics, family constellation, chromotherapy, clay therapy, hypnotherapy, hand imposition, ozone therapy and floral therapy. We only considered reviews that exclusively focused on one of these integrative interventions, rather than those addressing multiple interventions (called "umbrella" reviews).

Type of outcomes
We considered any clinical, social, laboratory or economic outcomes, as evaluated in the systematic reviews that were included.

Search for reviews
We carried out a sensitive systematic search in the Cochrane Database of Systematic Reviews cochrane-reviews-and-protocols-related-complementary-medicine.

Selection of systematic reviews
Two researchers (RLP and COC) independently screened and evaluated all records retrieved through the systematic search, to confirm their eligibility in accordance with the inclusion criteria.
Any disagreements were resolved by consulting a third author (RR or DVP).

Presentation of the results
We presented a summary of the reviews included, through a narrative approach (qualitative synthesis). The key points considered were the respective PICOs (population, intervention, comparator and outcomes), methods for SR and meta-analyses, quality of primary studies included, quality of the body of the evidence for each outcome, and applicability. When multiple interventions were addressed by a single SR, we considered only those relevant for the present study.

Results from systematic reviews
The 16 systematic reviews included related to four integrative practices: apitherapy (four SRs), aromatherapy (four SRs), hypnotherapy (six SRs) and ozone therapy (two SRs). In relation to the other six integrative practices (bioenergetics, family constellation, chromotherapy, clay therapy, hand imposition and flower therapy), no SR was retrieved through the search strategy and, therefore, no conclusion can be presented regarding their efficacy or safety.
The main findings from the SRs included and the quality of the evidence (based on the GRADE approach) are presented in Table 2. A brief summary of each SR is presented below.

Apitherapy
Apitherapy refers to the use of byproducts from bees (honey, propolis or apitoxins) to promote health or as a treatment option for diseases. 19 It is a broad term, including different practices ranging from topical use of honey as a wound treatment to systemic use of processed apitoxins for immunomodulation.

Honey as a topical treatment for wounds
This review 3 assessed the effects of honey, compared with alternative wound dressings and topical treatments, on the healing of acute and/or chronic wounds. It included 26 randomized clinical trials (RCTs, n = 3,011 participants). The RCTs included evaluated the effects of honey on: • minor acute wounds (3 RCTs); • burns (11 RCTs); • different chronic wounds including venous leg ulcers (10 RCTs); • diabetic foot ulcers (2 RCTs); • infected postoperative wounds, pressure injuries, cutaneous leishmaniasis and Fournier's gangrene (1 RCT each); and In this table, we only presented the results of systematic reviews that included studies that provided useful data. Thus, systematic reviews with no studies or with studies not containing any usable data were not included in this table. *GRADE (Grading of Recommendations Assessment, Development and Evaluation) has the aim of assessing the quality of the body of evidence. The evidence regarding a given outcome is assessed as having high quality (very high confidence in the results, i.e. the estimated effect is close to the true effect); moderate quality (it is very likely that the estimated effect is close to the real effect, but there is a possibility that it is not); low quality (the confidence in the effect estimate is limited); or very low quality (the true effect is likely to be substantially different from the estimate effect). • burns treated with honey heal more quickly than those treated with silver sulfadiazine (WMD -5.12 days; 95% CI -9.51 to -0.73; four RCTs; 332 participants; very low quality of evidence).
• burns treated with honey presented lower risk of adverse events than the silver sulfadiazine group (RR 0.29; 95% CI 0.20 to 0.42; six RCTs; 412 participants; high quality of evidence).
All other evidence was sparse, and its quality was downgraded because of risk of bias and imprecision. There was high diver-  • Use of honey was associated with reduced frequency of coughing, in comparison with placebo (MD -1.85; 95% CI -3.36 to -0.33; one RCT; 300 participants; high quality of evidence).
• There was no difference between use of honey and use of dextromethorphan (MD -0.07; 95% CI -1.07 to 0.94; two RCTs; 149 participants; moderate quality of evidence). • Use of honey was associated with reduced frequency of coughing in comparison with diphenhydramine (MD -0.57; 95% CI -0.90 to -0.24; one RCT; 80 participants; low quality of evidence).
Although some results indicate that use of honey may be associated with better results than those obtained through no treatment, placebo or diphenhydramine, caution should be used until solid recommendations for practice can be issued. All the available evidence was based on small RCTs, and the follow-up of some RCTs was only for one night after the intervention. It needs to be borne in mind also that the primary outcome was based on a scale: the minimum clinically relevant difference needs to be investigated and considered when recommending honey for symptomatic relief of coughing. Although some RCTs presented data regarding adverse events, no significant difference between the groups was reported. For further details and to access all analyses, refer to the original abstract, available from: http://cochranelibrary-wiley. com/doi/10.1002/14651858.CD007094.pub4/full.

Venom immunotherapy for preventing allergic reactions to insect stings
This review 5

Honey and lozenges for children with nonspecific coughs
This review 6

Aromatherapy
Aromatherapy is any type of treatment that involves use of essential oils. These might be obtained from herbs, flowers or other plants. 19 The compounds can be administered topically or through inhalation or water immersion.

Aromatherapy for treatment of postoperative nausea and vomiting
This review 7 aimed to assess the efficacy and safety of aromatherapy for treatment of postoperative nausea and vomiting.
Compared with placebo, aromatherapy reduced the use of rescue antiemetic medication (RR 0.60; 95% CI 0.37 to 0.97; seven RCTs; 609 participants; low quality of evidence). No difference between the groups was found regarding the following outcomes: Comparison of isopropyl alcohol aromatherapy with placebo showed that this treatment provided benefits regarding the following outcomes: • time (in minutes) to 50% reduction of nausea score (SMD -1.10 minutes; 95% CI -1.43 to -0.78; 3 RCTs; 176 participants; moderate quality of evidence); and • proportion of patients requiring antiemetics (RR 0.67; 95% CI 0.46 to 0.98; four RCTs; 215 participants; moderate quality of evidence).
No difference was found between the groups regarding patient satisfaction (RR 1.12; 95% CI 0.62 to 2.03; two RCTs; 172 participants; very low quality of evidence).
The overall methodological quality of the studies was considered low by the review authors. The adverse events were poorly reported, and no data were pooled. They considered that further studies would be imperative for solid conclusions to be drawn for practice. For further details and to access all analyses, refer to the original abstract, available from: http://cochranelibrary-wiley.com/ doi/10.1002/14651858.CD007598.pub3/full.

Aromatherapy for dementia
This review 8

Massage plus aromatherapy for symptom relief in people with cancer
This review 9 assessed the effects of massage with or without aromatherapy on relief of symptoms in people with cancer. Only two small RCTs (n = 117 participants) were included, and these pro-

Aromatherapy for pain management in labor
This review 10

Bioenergetics
Bioenergetic analysis is a specific form of body psychotherapy.
The bioenergetic approach has the aim of functioning through verbalization, corporal education and respiration techniques. 19 Our search strategy did not retrieve any Cochrane systematic review addressing this intervention.

Chromotherapy
Chromotherapy or color therapy is a therapeutic technique that uses colors of the electromagnetic spectrum. The principle is that each color has an effect on the body and this may be converted into a therapeutic approach. 19 Our search strategy did not retrieve any Cochrane systematic review addressing this intervention.

Family constellation
Family constellation is a psychotherapeutic method that aims to help patients by identifying hidden and transgenerational patterns of behavior in the family structure. It has the aim of leading towards resolution of conflicts within the family unit and within the individual perspective. 19 Our search strategy did not retrieve any Cochrane systematic review addressing this intervention.

Flower therapy
Flower therapy is a therapeutic approach that uses flowerderived essences. There is a theory that the use of floral therapy might act on mental state and emotions. 19 Our search strategy did not retrieve any Cochrane systematic review addressing this intervention.

Geotherapy
Geotherapy is defined as therapeutic use of a mixture of clay minerals and water in the form of cataplasm or mud baths applied to the skin. 19 It is empirically used in esthetics and in treating dermatological and rheumatological diseases. Our search strategy did not retrieve any Cochrane systematic review addressing this intervention.

Hypnotherapy
The term hypnotherapy refers to a group of techniques that uses hypnosis to treat health-related conditions. It assumes that through concentration and relaxation maneuvers, the patient may be able to change undesired conditions and behaviors. 19

Hypnotherapy for treatment of irritable bowel syndrome
This review 11

Hypnosis for induction of labor
This review 13

Hypnosis for pain management during labor and childbirth
This review 14 evaluated the effects of hypnosis for pain management in childbirth and labor. Seven RCTs and quasi-controlled trials (n = 1,213 participants) were included. They compared the use of hypnosis during or before labor versus placebo, no treatment or use of any analgesic drug or technique (control groups).
The use of pharmacological pain relief or anesthesia was lower in the group that received self-hypnosis or hypnotherapy, com-

Hypnosis for schizophrenia
This review 15 assessed the efficacy and safety of hypnosis for people with schizophrenia or schizophrenia-like illnesses, compared with any other treatment or standard therapy. Three RCTs were included (n = 149 participants). The main outcomes that the review aimed to investigate were: number of participants who dropped out before completion of the study; mental score, evaluated using the brief psychiatric rating scale (BPRS); movement disorders; and neurocognitive function.

Imposition of hands
Imposition of hands is, as defined in the Brazilian Ministry of Health's Glossary for Integrative and Complementary Practices in Healthcare, "a secular therapeutic practice that implies a meditative effort to transfer vital energy (such as Qi or prana, i.e. a universal vital energy that permeates the cosmos and constitutes all that exists) through the hands, in order to re-establish the equilibrium of the human energy field, thereby assisting in the health-disease process. " It is believed that imposition of hands could be beneficial for decreasing the levels of pain, depression and anxiety. 19 Our search strategy did not retrieve any Cochrane systematic review addressing this intervention.

Ozone therapy
Ozone is a molecule composed of three oxygen atoms. It has an unstable structure that makes it a powerful oxidant that can be administered in precise therapeutic doses. Some authors have claimed that it has health benefits under a variety of conditions characterized by hypoxic and ischemic syndromes. 20

Ozone therapy for treating foot ulcers in people with diabetes
This review 17

Ozone therapy for treating dental caries
This review 18 assessed the efficacy and safety of ozone therapy for controlling the progression of dental caries. Three RCTs were included (n = 137 participants). The authors of this SR aimed to evaluate the progression of caries in unrestored cases, use of further conventional treatment, time to intervention, cost, patient satisfaction and adverse events. All three RCTs included in this review evaluated local outcomes that the authors did not consider to be suitable for data pooling, so they did not do this.

DISCUSSION
This overview of reviews included 16 systematic reviews (SRs) that assessed the use of 4 out of the 10 integrative practices that were recently added to the procedures available through the Brazilian public healthcare system (SUS). The specific topics found were apitherapy (four SRs), aromatherapy (four SRs), hypnotherapy (six SRs) and ozone therapy (two SRs). No Cochrane SRs was found regarding bioenergetics, family constellation, chromotherapy, geotherapy, flower therapy or hand imposition.
Overall, the Cochrane reviews included reported high-quality evidence regarding some outcomes from the use of apitherapy.
All other evidence that was reported ranged in quality from unknown to moderate.
Honey dressings seemed to have some benefit over conventional dressings for the time needed to achieve partial healing of burn wounds, although this could be considered to be a surrogate outcome (if total healing were taken to be the clinically relevant outcome instead). Use of honey also seemed to reduce the frequency of coughing among children with acute coughs. Additionally, use of bee venom therapy seemed to prevent systematic allergic reactions to insect stings.
This overview made it clear that there are uncertainties regarding the efficacy and safety of the ten integrative practices that have recently been added to the procedures available through the Brazilian public healthcare system. Cochrane SRs are considered by many people to be the gold standard for evaluation of interventions within healthcare. Despite our wide-ranging search in the Cochrane database and broad inclusion criteria, we found that there was a lack of SRs investigating many topics (SRs were only available in relation to four out of these ten topics).
The absence of SRs relating to these topics may be indirectly indicative of the lack of controlled experimental studies assessing integrative practices. All of these practices need to be considered in the same way as any other intervention. There may have benefits, no effect or harm after their use. Any intervention, including integrative practices, is subject to adverse events and the safety component needs to be assessed in any evaluation. This review has some limitations. Our search was conducted in a single database, even though the Cochrane Library is recognized as the most important database of systematic reviews. The limited data available on each topic is a consequence of the small number of studies, and the low quality of the evidence relates to the small sample sizes and risk of bias of the RCTs. Another point that should be noted is the huge variety of techniques for each integrative and complementary health practice that were considered in the primary studies that were included in these systematic reviews, which led to difficulty in identifying the overall effect of each intervention.
Regarding practical implications, except for a single case (apitherapy, i.e. specifically use of honey for partial healing of wound burns and for treating acute coughs; and bee venom therapy for preventing allergic reactions to insect stings), the use of these ten integrative practices that were recently incorporated into SUS does not seem to be supported by adequate evidence found in Cochrane SRs. Thus, for many integrative practices, no randomized clinical trial was found. This does not mean that no benefit exists, but it does mean that huge uncertainties remain, regarding the benefits and harm associated with use of such interventions.
Hence, it appears that the incorporation of these ten integrative practices into SUS is in disagreement with Brazilian Federal law number 12,401 (of April 2011), which establishes that health technologies, including medicines, orthoses, prostheses, diagnostic and therapeutic procedures and health care, can be incorporated into the public healthcare system (SUS) only when the National Commission for Incorporation of Technologies (CONITEC) finds scientific evidence of efficacy, accuracy, effectiveness and safety in relation to the drug, product or procedure under analysis that is accepted by the institution in charge of registration or authorization for use. 21 Regarding the implications for research, this review found out that much remains to be done in relation to establishing what effects the IPs addressed here have for healthcare. RCTs with high methodological quality are recommended before any health intervention is brought into routine prescription and use. Subsequently, cost-effectiveness studies will need to be developed for the integrative practices that were proven to be effective and safe (as findings from RCTs). Economic studies analyzing these integrative practices in terms of their consequences for health and their economic burden are also worthwhile.

CONCLUSION
This review identified 16 Cochrane systematic reviews that provided evidence, of a range of quality, in relation to ten new integrative practices that were recently incorporated into the Brazilian public healthcare system (SUS). Except for a few cases of apitherapy (honey dressings for partial healing of wound burns, honey to reduce coughing among children with acute coughs and bee venom to prevent allergic reactions to insect stings), none of the integrative practices addressed by the present review are supported by Cochrane SRs, because • there is a lack of primary studies; or • no Cochrane SRs exist (bioenergetics, chromotherapy, family constellation, flower therapy, geotherapy and imposition of hands); or • the evidence found so far is insufficient for producing any sound conclusion. Evidence from additional sources regarding the effects of other integrative practices that have not been addressed by Cochrane SRs needs to be searched for.