Andrew Flower

Andrographis paniculata (Chuān Xīn Lián) for symptomatic relief of acute respiratory tract infections in adults and children: a systematic review and meta-analysis

Introduction Antimicrobial resistance (AMR) is a substantial threat to public health. Safe and effective alternatives are required to reduce unnecessary antibiotic prescribing. Andrographis Paniculata (A. Paniculata, Chuān Xīn Lián) has traditionally been used in Indian and Chinese herbal medicine for cough, cold and influenza, suggesting a role in respiratory tract infections (RTIs). This systematic review aimed to evaluate the clinical effectiveness and safety of A. Paniculata for symptoms of acute RTIs (ARTIs). Materials and methods English and Chinese databases were searched from their inception to March 2016 for randomised controlled trials (RCTs) evaluating oral A. Paniculata without language barriers (Protocol ID: CRD42016035679). The primary outcomes were improvement in ARTI symptoms and adverse events (AEs). A random effects model was used to pool the mean differences and risk ratio with 95% CI reported. Methodological quality was evaluated using the Cochrane risk of bias tool; two reviewers independently screened eligibility and extracted data. Results Thirty-three RCTs (7175 patients) were included. Most trials evaluated A. Paniculata (as a monotherapy and as a herbal mixture) provided commercially but seldom reported manufacturing or quality control details. A. Paniculata improved cough (n = 596, standardised mean difference SMD: -0.39, 95% confidence interval CI [-0.67, -0.10]) and sore throat (n = 314, SMD: -1.13, 95% CI [-1.37, -0.89]) when compared with placebo. A. Paniculata (alone or plus usual care) has a statistically significant effect in improving overall symptoms of ARTIs when compared to placebo, usual care, and other herbal therapies. Evidence also suggested that A. Paniculata (alone or plus usual care) shortened the duration of cough, sore throat and sick leave/time to resolution when compared versus usual care. No major AEs were reported and minor AEs were mainly gastrointestinal. The methodological quality of included trials was overall poor. Conclusions A. Paniculata appears beneficial and safe for relieving ARTI symptoms and shortening time to symptom resolution. However, these findings should be interpreted cautiously owing to poor study quality and heterogeneity. Well-designed trials evaluating the effectiveness and potential to reduce antibiotic use of A. Paniculata are warranted.

Oral Chinese herbal medicine (CHM) as an adjuvant treatment during chemotherapy for non-small cell lung cancer: A systematic review

BACKGROUND Non-small cell lung cancer (NSCLC) remains a major global health problem because of its prevalence and poor prognosis. Treatment options are limited and there is a need to explore alternatives. This systematic review evaluates the role of Chinese herbal medicine (CHM) in association with chemotherapy for NSCLC. METHODS English and Chinese databases were searched for RCTs comparing CHM with conventional biomedical treatment or placebo. Papers were reviewed systematically and data were analysed using standard Cochrane software Revman 5. RESULTS Fifteen Chinese trials involving 862 participants met the inclusion criteria. All trials were of poor quality with a considerable risk of bias. There was a significant improvement in quality of life (QoL) (increased Karnofsky Performance Status) (RR 1.83, 95% CI 1.41-2.38, p<0.00001 for both stages III, IV only NSCLC and all stages NSCLC) and less anaemia (RR 0.37, 95% CI 0.15-0.91, p=0.03 for stages III, IV only NSCLC; p=0.005 for all stages NSCLC) and neutropenia (RR 0.42, 95% CI 0.22-0.82, p=0.01 for stages III, IV only NSCLC; p<0.00001 for all stages NSCLC) when CHM is combined with chemotherapy compared to chemotherapy alone. There was no significant difference in short term effectiveness and limited inconclusive data concerning long term survival. Five promising herbs have been identified. CONCLUSION It is possible that oral CHM used in conjunction with chemotherapy may improve QoL in NSCLC. This needs to be examined further with more rigorous methodology.

Comparison of effectiveness and safety between granules and decoction of Chinese herbal medicine: A systematic review of randomized clinical trials

BACKGROUND The clinical use of Chinese herbal medicine granules is gradually increasing. However, there is still no systematic review comparing the effectiveness and safety of granules with the more traditional method of herbal decoctions. METHOD A literature search was conducted using China National Knowledge Infrastructure Databases (CNKI), Chinese Science and Technology Periodical Database (VIP), China Biomedical Database web (CBM), Wanfang Database, PubMed, and the Cochrane Library until March 10, 2011. Clinical controlled trials (CCTs) including randomized trials (RCTs) comparing the effectiveness and safety between Chinese herbal medicine granules and decoction were included. Two authors conducted the literature searches, and extracted data independently. The assessment of methodological quality of RCTs was based on the risk of bias from the Cochrane Handbook, and the main outcome data of trials were analyzed by using RevMan 5.0 software. Risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) were used as effect measure. RESULTS 56 clinical trials (n=9748) including 42 RCTs and 14 CCTs were included, and all trials were conducted in China and published in Chinese literature. 40 types of diseases and 15 syndromes of traditional Chinese medicine (TCM) were reported. Granules were provided by pharmaceutical companies in 13 trials. The included RCTs were of generally low methodological quality: 7 trials reported adequate randomization methods, and 2 of these reported allocation concealment. 10 trials used blinding, of which 5 trials used placebo which were delivered double blind (blinded participants and practitioners). 98.2% (55/56) of studies showed that there was no significant statistical difference between granules and decoctions of Chinese herbal medicine for their effectiveness. No severe adverse effects in either group were reported. CONCLUSIONS Due to the poor methodological quality of most of the included trials, it is not possible to reach a definitive conclusion whether both Chinese herbal medicine granules and decoctions have the same degree of effectiveness and safety in clinical practice, but this preliminary evidence supports the continued use of granules in clinical practice and research. Standardization of granules and further more rigorous pharmacological, toxicological and clinical studies are needed to demonstrate the equivalence with decoctions.

Can Chinese herbal medicine improve outcomes of in vitro fertilization? A systematic review and meta-analysis of randomized controlled trials.

Background A large number of infertile couples are choosing Chinese herbal medicine (CHM) as an adjuvant therapy to improve their success when undergoing in vitro fertilization (IVF). There is no systematic review to evaluate the impact of CHM on the IVF outcomes. Objective To evaluate the effectiveness of CHM with concurrent IVF versus IVF alone on the outcomes of IVF and its safety. Methods The protocol of this study is registered at PROSPERO. Eligible RCTs searched from 8 databases which compared a combination of CHM and IVF with IVF alone were included. Two authors independently selected studies, extracted data and assessed methodological quality. Meta-analysis of RCTs was conducted if there was non-significant heterogeneity (evaluated by I2 test) among trials. All statistical analysis was performed using RevMan 5.1 software. Results Twenty trials involving 1721 women were included in the meta-analysis. Three trials were evaluated as having an unclear risk of bias. The remaining trials were evaluated as having a high risk of bias. Combination of CHM and IVF significantly increases clinical pregnancy rates (OR 2.04, 95%CI 1.67 to 2.49, p<0.00001) and ongoing pregnancy rates (OR 1.91, 95%CI 1.17 to 3.10, p = 0.009). Use of CHM after embryo transfer had no better outcome in reducing the rate of ovarian hyper stimulation syndrome (OR 0.39, 95%CI 0.14 to 1.11, p = 0.08). Conclusions This meta-analysis showed that combination of IVF and CHM used in the included trials improve IVF success, however due to the high risk of bias observed with the trials, the significant differences found with the meta-analysis are unlikely to be accurate. No conclusion could be drawn with respect to the reproductive toxicity of CHM. Further large randomized placebo controlled trials are warranted to confirm these findings before recommending women to take CHM to improve their IVF success.

Unique Aspects of Herbal Whole System Research

INTRODUCTION Whole systems of healthcare offer unique methodological and theoretical challenges for researchers. Herbalism has its own set of methodological and philosophical research issues that are beyond those presented for whole system research in general. It was our objective to explore various conceptual and methodological issues surrounding whole system herbal research. METHODS An International Society for Complementary Medicine Research workshop, Challenges in Herbal Whole System Research, was presented. Starting from a definition of herbalism, the most important challenges to herbal whole system research were elicited with inputs from both the workshop presenters and the audience. RESULTS Five major challenges unique to herbal whole system research were identified: (1) defining herbalists and herbalism, (2) the role of the natural products industry in herbal research, (3) designing placebos and delivering active herbal treatments as given by herbalists, (4) researching the herb as a living entity, and (5) designing trials to investigate and develop multicomponent herbal therapies. CONCLUSIONS Unique methods and theoretical frameworks are required to design studies of herbalism. Solutions to these methodological challenges need to be addressed to conduct research that examines herbal systems of medicine versus conducting trials on individual herbs given out of their original therapeutic context.

The Context and Meaning of Placebos for Complementary Medicine

Calls for placebo-controlled randomised trials in complementary and alternative medicine (CAM) are entirely reasonable. However, they present major methodological problems, particularly when we understand so little about the underlying biological mechanisms involved for many of these therapies. Designing a placebo in CAM is frequently dependent on unsubstantiated assumptions about the specificity of a particular CAM intervention. In this paper we address the development and application of placebos to clinical trials of homeopathy, acupuncture, kinesiology, Chinese herbal medicine and healing. Each therapy-based vignette is authored by a researcher from the Complementary and Integrated Medicine Research Unit at the University of Southampton who has specific expertise in the field. The essential research question within this review is; can we legitimately claim to have placebos for these particular CAM interventions? In some areas of CAM the debate has become very involved and sophisticated, for instance in acupuncture but for other areas, such as healing, our understanding of placebos is currently limited and very naïve. For instance, if acupuncture is not point specific, then many so-called ‘placebo-controlled’ acupuncture trials are both misconceived and misleading. We have addressed this debate in what we hope is a thoughtful and rigorous manner with a view to developing realistic, reliable and credible placebos for randomised controlled studies when and where possible. However, our conclusions suggest that we are some way from developing valid, credible and reliable placebos for most CAM therapies.

A feasibility study exploring the role of Chinese herbal medicine in the treatment of endometriosis.

BACKGROUND Endometriosis is a common and disabling gynecologic condition affecting between 5% and 15% of women of childbearing age. Conventional medical intervention has unpleasant side-effects, and symptoms frequently return after treatment. Preliminary evidence suggests Chinese herbal medicine (CHM) may contribute to the treatment of endometriosis. OBJECTIVES The aims of this study were to test the feasibility of a novel methodology for investigating individualized decoctions of CHM rigorously and to gather preliminary data on the treatment effect of CHM for a larger definitive trial. DESIGN This was a 16-week prospective, double blinded, randomized controlled trial of 40 women with laparoscopically confirmed endometriosis. SETTINGS The trial was conducted at a private CHM clinic in Hove (U.K.) and at a National Health Service outpatient clinic in London (U.K.). INTERVENTIONS Participants were initially randomized to either wait-list control (WLC) or treatment groups to receive either individualized CHM decoctions or a therapeutically inert placebo decoction. OUTCOME MEASURES Four 10-cm visual analogue scales (VAS) were used to measure menstrual pain, daily pain, and pain on intercourse and bowel movement; these measurements were recorded weekly. The Endometriosis Health Profile-30 (EHP-30) endometriosis-specific quality-of-life questionnaire was completed at the beginning and at the end of the trial. The Measure Yourself Medical Outcomes Profile (MYMOP) a patient-centered health questionnaire was completed monthly. Liver and renal function was measured at 0, 4, 8, and 16 weeks. RESULTS Twenty-eight (28) women completed the trial. High dropout rates led to the suspension of the WLC. Randomization, double blinding, and allocation concealment was achieved successfully. Adjusted mean differences favored the active treatment in the EHP-30 and MYMOP scores. VAS scores favored the active treatment for relief of menstrual pain and the placebo group for reduction of daily pain. CONCLUSIONS the methodology successfully allowed individualized CHM decoctions to be tested rigorously. There are nonspecific contextual effects from CHM that require further investigation. Provisional data were generated to warrant a larger, more-definitive study.

Developing clinical practice guidelines for Chinese herbal treatment of polycystic ovary syndrome: a mixed-methods modified Delphi study

OBJECTIVES Preliminary evidence suggests Chinese herbal medicine (CHM) could be a viable treatment option for polycystic ovary syndrome (PCOS). Prior to conducting a clinical trial it is important to consider the characteristics of good clinical practice. This study aims to use professional consensus to establish good clinical practice guidelines for the CHM treatment of PCOS. DESIGN AND SETTING CHM practitioners participated in a mixed-methods modified Delphi study involving three rounds of structured group communication. Round 1 involved qualitative interviews with practitioners to generate statements regarding good clinical practice. In round 2, these statements were distributed online to the same practitioners to rate their agreement using a 7-point Likert scale, where group consensus was defined as a median rating of ≥5. Statements reaching consensus were accepted for consideration onto the guideline whilst those not reaching consensus were re-distributed for consideration in round 3. Statements presented in the guidelines were graded from A (strong consensus) to D (no consensus) determined by median score and interquartile range. RESULTS 11 CHM practitioners in the UK were recruited. After three Delphi rounds, 91 statement items in total had been considered, of which 89 (97.8%) reached consensus and 2 (2.2%) did not. The concluding set of guidelines consists of 85 items representing key features of CHM prescribing for PCOS. CONCLUSIONS These guidelines can be viewed as an initial framework that captures fundamental principles of good clinical practice for CHM.

Effectiveness guidance document (EGD) for Chinese medicine trials: A consensus document

BackgroundThere is a need for more Comparative Effectiveness Research (CER) on Chinese medicine (CM) to inform clinical and policy decision-making. This document aims to provide consensus advice for the design of CER trials on CM for researchers. It broadly aims to ensure more adequate design and optimal use of resources in generating evidence for CM to inform stakeholder decision-making.MethodsThe Effectiveness Guidance Document (EGD) development was based on multiple consensus procedures (survey, written Delphi rounds, interactive consensus workshop, international expert review). To balance aspects of internal and external validity, multiple stakeholders, including patients, clinicians, researchers and payers were involved in creating this document.ResultsRecommendations were developed for “using available data” and “future clinical studies”. The recommendations for future trials focus on randomized trials and cover the following areas: designing CER studies, treatments, expertise and setting, outcomes, study design and statistical analyses, economic evaluation, and publication.ConclusionThe present EGD provides the first systematic methodological guidance for future CER trials on CM and can be applied to single or multi-component treatments. While CONSORT statements provide guidelines for reporting studies, EGDs provide recommendations for the design of future studies and can contribute to a more strategic use of limited research resources, as well as greater consistency in trial design.

How women manage recurrent urinary tract infections: an analysis of postings on a popular web forum

BackgroundRecurrent urinary tract infections (RUTIs) are commonly presented by women in primary care. In order to explore the poorly described experience of women with RUTIs a qualitative study was conducted that analysed data from a publically accessible internet-based self-help forum.MethodsQualitative Description was used to analyse the text with an emphasis on using the naturalistic language of the informants to portray their perceptions and experiences of RUTIs. Individual codes were identified inductively and grouped according to common ideas into related categories, before being incorporated into five main themes.ResultsWomen of diverse ages and geographical location contributed to the website. Themes were identified that vividly explored the atypical symptomatology of RUTIs, the serious impact it had on many aspects of women’s lives, different attitudes to treatments options such as antibiotics, the use of unorthodox approaches such as complementary and alternative medicines (CAM) and contrasting experiences of medical practitioners.ConclusionA web-based analysis can vividly capture the views of a diverse population. RUTIs can have a disabling effect on women’s health, their intimate and social relationships, self-esteem, and capacity for work. Further research is required to clarify the wider relevance of the qualitative themes identified, to identify key elements of good practice, and to provide a more rigorous assessment of CAM interventions.