Chinese herbal medicine for treating recurrent urinary tract infections in women.

BACKGROUND: Acute urinary tract infection (UTI) is a common bacterial infection that affects 40% to 50% of women. Between 20% and 30% of women who have had a UTI will experience a recurrence, and around 25% will develop ongoing recurrent episodes with implications for individual well-being and healthcare costs. Prophylactic antibiotics can prevent recurrent UTIs but there are growing concerns about microbial resistance, side effects from treatment and lack of long-term benefit. Consequently, alternative treatments are being investigated. Chinese herbal medicine (CHM) has a recorded history of treating UTI symptoms and more recent research suggests a potential role in the management of recurrent UTIs. This review aimed to evaluate CHM for recurrent UTI. OBJECTIVES: This review assessed the benefits and harms of CHM for the treatment of recurrent UTIs in adult women, both as a stand-alone therapy and in conjunction with other pharmaceutical interventions. SEARCH METHODS: We searched the Cochrane Kidney and Transplant's Specialised Register to 7 May 2015 through contact with the Trials Search Co-ordinator, using search terms relevant to this review. We also searched AMED, CINAHL and the Chinese language electronic databases Chinese BioMedical Literature Database (CBM), China Network on Knowledge Infrastructure (CNKI), VIP and Wan Fang Databases to July 2014. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing treatments using CHM with either an inactive placebo or conventional biomedical treatment. RCTs comparing different CHM strategies and treatments were eligible for inclusion. Quasi-randomised studies were excluded. DATA COLLECTION AND ANALYSIS: Data extraction was carried out independently by two authors. Where more than one publication of one study existed, these were grouped and the publication with the most complete data was used in the analyses. Where relevant outcomes were only published in earlier versions these data were used. All meta-analyses were performed using relative risk (RR) for dichotomous outcomes with 95% confidence intervals (CI). MAIN RESULTS: We included seven RCTs that involved a total of 542 women; of these, five recruited post-menopausal women (aged from 56 to 70 years) (422 women). We assessed all studies to be at high risk of bias. Meta-analyses comparing the overall effectiveness of treatments during acute phases of infection and rates of recurrence were conducted. Analysis of three studies involving 282 women that looked at CHM versus antibiotics suggested that CHM had a higher rate of effectiveness for acute UTI (RR 1.21, 95% CI 1.11 to 33) and reduced recurrent UTI rates (RR 0.28, 95% CI 0.09 to 0.82). Analysis of two studies involving 120 women that compared CHM plus antibiotics versus antibiotics alone found the combined intervention had a higher rate of effectiveness for acute UTI (RR 1.24, 95% CI 1.04 to 1.47) and resulted in lower rates of recurrent infection six months after the study (RR 0.53, 95% CI 0.35 to 0.80).One study comparing different CHM treatments found Er Xian Tang was more effective in treating acute infection in post-menopausal women than San Jin Pian (80 women: RR 1.28, 95% CI 1.03 to 1.57). Analysis showed that active CHM treatments specifically formulated for recurrent UTI were more effective in reducing infection incidence than generic CHM treatments that were more commonly used for acute UTI (RR 0.40, 95% CI 0.21 to 0.77).Only two studies undertook to report adverse events; neither reported the occurrence of any adverse events. AUTHORS' CONCLUSIONS: Evidence from seven small studies suggested that CHM as an independent intervention or in conjunction with antibiotics may be beneficial for treating recurrent UTIs during the acute phase of infection and may reduce the recurrent UTI incidence for at least six months post-treatment. CHM treatments specifically formulated for recurrent UTI may be more effective than herbal treatments designed to treat acute UTI. However, the small number and poor quality of the included studies meant that it was not possible to formulate robust conclusions on the use of CHM for recurrent UTI in women either alone or as an adjunct to antibiotics.

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

BACKGROUND: Recurrent 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. METHODS: Qualitative 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. RESULTS: Women 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. CONCLUSION: A 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.

Chinese herbal medicine for endometriosis.

BACKGROUND: Endometriosis is characterized by the presence of tissue that is morphologically and biologically similar to normal endometrium in locations outside the uterus. Surgical and hormonal treatment of endometriosis have unpleasant side effects and high rates of relapse. In China, treatment of endometriosis using Chinese herbal medicine (CHM) is routine and considerable research into the role of CHM in alleviating pain, promoting fertility, and preventing relapse has taken place.This review is an update of a previous review published in the Cochrane Database of Systematic Reviews 2009, issue No 3. OBJECTIVES: To review the effectiveness and safety of CHM in alleviating endometriosis-related pain and infertility. SEARCH METHODS: We searched the Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library) and the following English language electronic databases (from their inception to 31/10/2011): MEDLINE, EMBASE, AMED, CINAHL, and NLH.We also searched Chinese language electronic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Sci & Tech Journals (VIP), Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), and Chinese Medical Current Contents (CMCC). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving CHM versus placebo, biomedical treatment, another CHM intervention; or CHM plus biomedical treatment versus biomedical treatment were selected. Only trials with confirmed randomisation procedures and laparoscopic diagnosis of endometriosis were included. DATA COLLECTION AND ANALYSIS: Risk of bias assessment, and data extraction and analysis were performed independently by three review authors. Data were combined for meta-analysis using relative risk (RR) for dichotomous data. A fixed-effect statistical model was used, where appropriate. Data not suitable for meta-analysis were presented as descriptive data. MAIN RESULTS: Two Chinese RCTs involving 158 women were included in this review. Both these trials described adequate methodology. Neither trial compared CHM with placebo treatment.There was no evidence of a significant difference in rates of symptomatic relief between CHM and gestrinone administered subsequent to laparoscopic surgery (95.65% versus 93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one RCT). The intention-to-treat analysis also showed no significant difference between the groups (RR 1.04, 95% CI 0.91 to 1.18). There was no significant difference between the CHM and gestrinone groups with regard to the total pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to 1.59, one RCT).CHM administered orally and then in conjunction with a herbal enema resulted in a greater proportion of women obtaining symptomatic relief than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively). Overall, 100% of women in all the groups showed some improvement in their symptoms.Oral plus enema administration of CHM showed a greater reduction in average dysmenorrhoea pain scores than did danazol (mean difference (MD) -2.90, 95% CI -4.55 to -1.25; P < 0.01). Combined oral and enema administration of CHM also showed a greater improvement measured as the disappearance or shrinkage of adnexal masses than with danazol (RR 1.70, 95% CI 1.04 to 2.78). For lumbosacral pain, rectal discomfort, or vaginal nodules tenderness, there was no significant difference between CHM and danazol. AUTHORS' CONCLUSIONS: Post-surgical administration of CHM may have comparable benefits to gestrinone but with fewer side effects. Oral CHM may have a better overall treatment effect than danazol; it may be more effective in relieving dysmenorrhoea and shrinking adnexal masses when used in conjunction with a CHM enema. However, more rigorous research is required to accurately assess the potential role of CHM in treating endometriosis.

Chinese herbal medicine for endometriosis.

BACKGROUND: Endometriosis is characterized by the presence of tissue that is morphologically and biologically similar to normal endometrium in locations outside the uterus. Surgical and hormonal treatment of endometriosis have unpleasant side effects and high rates of relapse. In China, treatment of endometriosis using Chinese herbal medicine (CHM) is routine and considerable research into the role of CHM in alleviating pain, promoting fertility, and preventing relapse has taken place. OBJECTIVES: To review the effectiveness and safety of CHM in alleviating endometriosis-related pain and infertility. SEARCH STRATEGY: We searched the Menstrual Disorders and Subfertility Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library) and the following English language electronic databases (from their inception to the present): MEDLINE, EMBASE, AMED, CINAHL, NLH on the 30/04/09.We also searched Chinese language electronic databases: Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Chinese Sci & Tech Journals (VIP), Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS), and Chinese Medical Current Contents (CMCC). SELECTION CRITERIA: Randomised controlled trials (RCTs) involving CHM versus placebo, biomedical treatment, another CHM intervention, or CHM plus biomedical treatment versus biomedical treatment were selected. Only trials with confirmed randomisation procedures and laparoscopic diagnosis of endometriosis were included. DATA COLLECTION AND ANALYSIS: Risk of bias assessment, and data extraction and analysis were performed independently by three review authors. Data were combined for meta-analysis using relative risk (RR) for dichotomous data. A fixed-effect statistical model was used, where appropriate. Data not suitable for meta-analysis are presented as descriptive data. MAIN RESULTS: Two Chinese RCTs involving 158 women were included in this review. Both these trials described adequate methodology. Neither trial compared CHM with placebo treatment.There was no evidence of a significant difference in rates of symptomatic relief between CHM and gestrinone administered subsequent to laparoscopic surgery (95.65% versus 93.87%; risk ratio (RR) 1.02, 95% confidence interval (CI) 0.93 to 1.12, one RCT). The intention-to-treat analysis also showed no significant difference between the groups (RR 1.04, 95% CI 0.91 to 1.18). There was no significant difference between the CHM and gestrinone groups with regard to the total pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to 1.59, one RCT).CHM administered orally and then in conjunction with a herbal enema resulted in a greater proportion of women obtaining symptomatic relief than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively).Overall, 100% of women in all the groups showed some improvement in their symptoms.Oral plus enema administration of CHM showed a greater reduction in average dysmenorrhoea pain scores than did danazol (mean difference (MD) -2.90, 95% CI -4.55 to -1.25; P < 0.01).Combined oral and enema administration of CHM showed a greater improvement, measured as the disappearance or shrinkage of adnexal masses, than with danazol (RR 1.70, 95% CI 1.04 to 2.78). For lumbosacral pain, rectal discomfort, or vaginal nodules tenderness, there was no significant difference either between CHM and danazol. AUTHORS' CONCLUSIONS: Post-surgical administration of CHM may have comparable benefits to gestrinone but with fewer side effects. Oral CHM may have a better overall treatment effect than danazol; it may be more effective in relieving dysmenorrhea and shrinking adnexal masses when used in conjunction with a CHM enema. However, more rigorous research is required to accurately assess the potential role of CHM in treating endometriosis.

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 RUTI trial: A feasibility study exploring Chinese herbal medicine for the treatment of recurrent urinary tract infections.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) is a widely used traditional intervention that may have a role to play in addressing the global problem of antimicrobial resistance in conditions such as recurrent urinary tract infections (RUTIs). AIM OF THE STUDY: To evaluate the feasibility of administering standardised and individualised formulations of CHM for RUTIs as a Clinical Trial of an Investigational Medicinal Product (CTIMP) within primary care of the UKs National Health Service (NHS). MATERIALS AND METHODS: Regulatory approval was applied for a placebo controlled, double blinded randomised controlled feasibility trial comparing a) standardised CHM vs placebo administered via General practitioners, and b) individualised CHM vs placebo administered by an experienced CHM practitioner. Primary feasibility outcomes included: gaining regulatory approval, recruitment, randomisation, retention, safety and the relevance of outcomes measures. RESULTS: Regulatory approval for testing CHM as a CTIMP was successfully obtained. Recruitment to the trial was slow and non-NHS self help networks were required to find participants for the individualised arm (n = 31). Retention and data collection in the standardised arm (n-30) were problematic, but these were acceptable in the individualised arm. The use of a daily symptom diary was not a suitable outcome measure for women with continuous infection. Other measures showed promising preliminary data for the individualised arm on improvement in symptoms, and reduction in antibiotic use during and after the trial. CONCLUSION: CHM can fulfil the demanding requirements of a CTIMP study but it may not be feasible at this point in time to recruit and treat via NHS primary care. However acceptable rates of recruitment and retention via self-help groups and promising preliminary results in the individualised arm suggest it would be worth testing this approach in a full trial.

Correction: Andrographis paniculata (Chuan Xin Lián) for symptomatic relief of acute respiratory tract infections in adults and children: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pone.0181780.].

Seeking an oracle: using the Delphi process to develop practice guidelines for the treatment of endometriosis with Chinese herbal medicine.

BACKGROUND: For most complementary and alternative medicine interventions, the absence of a high-quality evidence base to define good practice presents a serious problem for clinicians, educators, and researchers. The Delphi process may offer a pragmatic way to establish good practice guidelines until more rigorous forms of assessment can be undertaken. OBJECTIVES: To use a modified Delphi to develop good practice guidelines for a feasibility study exploring the role of Chinese herbal medicine (CHM) in the treatment of endometriosis. To compare the outcomes from Delphi with data derived from a systematic review of the Chinese language database. DESIGN: An expert group was convened for a three-round Delphi that initially produced key statements relating to the CHM diagnosis and treatment of endometriosis (round 1) and then anonymously rated these on a 1-7 Likert scale (rounds 2 and 3). Statements with a median score of 5 and above were regarded as demonstrating positive group consensus. The differential diagnoses within Chinese Medicine and rating of the clinical value of individual herbs were then contrasted with comparable data from a review of Chinese language reports in the Chinese Biomedical Retrieval System (1978-2002), and China Academy of Traditional Chinese Medicine (1985-2002) databases and the Chinese TCM and magazine literature (1984-2004) databases. RESULTS: Consensus (good practice) guidelines for the CHM treatment of endometriosis relating to common diagnostic patterns, herb selection, dosage, and patient management were produced. The Delphi guidelines demonstrated a high degree of congruence with the information from the Chinese language databases. CONCLUSIONS: In the absence of rigorous evidence, Delphi offers a way to synthesize expert knowledge relating to diagnosis, patient management, and herbal selection in the treatment of endometriosis. The limitations of the expert group and the inability of Delphi to capture the subtle nuances of individualized clinical decision-making limit the usefulness of this approach.

Standardised versus individualised multiherb Chinese herbal medicine for oligomenorrhoea and amenorrhoea in polycystic ovary syndrome: a randomised feasibility and pilot study in the UK.

OBJECTIVES: To explore feasibility of a randomised study using standardised or individualised multiherb Chinese herbal medicine (CHM) for oligomenorrhoea and amenorrhoea in women with polycystic ovary syndrome (PCOS), to pilot study methods and to obtain clinical data to support sample size calculations. DESIGN: Prospective, pragmatic, randomised feasibility and pilot study with participant and practitioner blinding. SETTING: 2 private herbal practices in the UK. PARTICIPANTS: 40 women diagnosed with PCOS and oligomenorrhoea or amenorrhoea following Rotterdam criteria. INTERVENTION: 6 months of either standardised CHM or individualised CHM, 16 g daily taken orally as a tea. MAIN OUTCOME MEASURES: Our primary objective was to determine whether oligomenorrhoea and amenorrhoea were appropriate as the primary outcome measures for the main study. Estimates of treatment effects were obtained for menstrual rate, body mass index (BMI), weight and hirsutism. Data were collected regarding safety, feasibility and acceptability. RESULTS: Of the 40 participants recruited, 29 (72.5%) completed the study. The most frequently cited symptoms of concern were hirsutism, weight and menstrual irregularity. Statistically significant improvements in menstrual rates were found at 6 months within group for both standardised CHM (mean difference (MD) 0.18±0.06, 95% CI 0.06 to 0.29; p=0.0027) and individualised CHM (MD 0.27±0.06, 95% CI 0.15 to 0.39; p<0.001), though not between group (p=0.26). No improvements were observed for BMI nor for weight in either group. Improvements in hirsutism scores found within group for both groups were not statistically significant between group (p=0.09). Liver and kidney function and adverse events data were largely normal. Participant feedback suggests changing to tablet administration could facilitate adherence. CONCLUSIONS: A CHM randomised controlled trial for PCOS is feasible and preliminary data suggest that both individualised and standardised multiherb CHMs have similar safety profiles and clinical effects on promoting menstrual regularity. These data will inform the design of a study in primary care that will incorporate an appropriate control. TRIAL REGISTRATION NUMBER: ISRCTN 31072075; Results.

Andrographis paniculata (Chuan Xin 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, Chuan Xin 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.

Uva-ursi extract and ibuprofen as alternative treatments of adult female urinary tract infection (ATAFUTI): study protocol for a randomised controlled trial.

BACKGROUND: Women with acute uncomplicated urine infection are usually treated with antibiotics. One trial has demonstrated that delayed antibiotic treatment offered without symptom relief results in a modest reduction in antibiotic use. There is some evidence that ibuprofen provides symptom relief and reduces antibiotic use. Uva-ursi, a herbal product, has a traditional use for urinary infection symptom relief. We set out to test: in adult women with suspected UTI who accept the delayed prescription strategy: Do NSAIDs or uva-ursi (a herbal product) provide relief from urinary symptoms and reduce antibiotic use. METHODS/DESIGN: Adult women with suspected urinary tract infection presenting to primary care will be randomised using a factorial trial design in which patients will be randomised to one of two interventions as below: Group 1 - Uva-ursi + advice to take ibuprofen Group 2 - Placebo + advice to take ibuprofen Group 3 - Uva-ursi + no advice to take ibuprofen Group 4 - Placebo + no advice to take ibuprofen Patients and physicians will be blinded to the randomised group for the herb. The main outcome is symptom severity at days 2-4 recorded in a validated, self-report diary used in previous studies. Secondary outcomes include antibiotic use and symptom duration. In total the trial will require 328 patients in order to achieve at least 90% power for the primary endpoint and 80% for the secondary endpoint. In accordance with CONSORT guidelines all comparative analyses will be conducted on an intention-to-treat basis using SPSS or similar package. DISCUSSION: The outcomes from this trial have the potential to modify the current approach to the management of acute urinary symptoms with less dependence on the use of antibiotics. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN43397016 . Registered on 11 February 2015.

Standardised Chinese herbal treatment delivered by GPs compared with individualised treatment administered by practitioners of Chinese herbal medicine for women with recurrent urinary tract infections (RUTI): study protocol for a randomised controlled trial.

BACKGROUND: In the UK, urinary tract infections (UTIs) are the most common bacterial infection presented by women in primary care. Recurrent urinary tract infections (RUTIs) are defined as three episodes of UTI in the last 12 months, or two episodes in the last 6 months. Between 20 and 30 % of women who have had one episode of UTI will have an RUTI, and approximately 25 % of these will develop subsequent recurrent episodes. RUTIs can have a significant negative effect on the quality of life, and have a high impact on health care costs as a result of outpatient visits, diagnostic tests and prescriptions. Chinese herbal medicine (CHM) has a recorded history of treatments for the symptoms of UTIs for more than 2000 years. More recent clinical research in China has provided some preliminary evidence that CHM can alleviate the symptoms of UTIs and reduce the rate of recurrence, but more rigorous investigation is required. METHODS/DESIGN: The RUTI trial is a double-blind, randomised, placebo-controlled, feasibility trial. A total of 80 women will be randomised to 'individualised' herbs prescribed by a Chinese herbal practitioner or to 'standardised' herbs provided by primary care clinicians. Both arms will have herbs for prevention of UTIs and treatment of acute episodes. Treatment duration is for 16 weeks. The primary outcomes are the number of episodes of recurrent UTIs during the trial period and in the 6 months of follow-up, and the number of days of symptoms rated moderately bad or worse based on patient diaries. Secondary outcomes will assess participant expectations and beliefs, adherence to the treatment, adverse events and health economics and provide quantitative and qualitative assessments of the impact of recurrent infections on the lives of women. DISCUSSION: The RUTI trial is the first instance of CHM delivered as a clinical trial of an investigatory medicinal product in the UK. This study provides important information regarding the feasibility and acceptability of researching and using CHM in Primary care. Once completed, it will provide provisional estimates of the variance of change in continuous outcomes to inform a power calculation for a larger, more definitive trial. TRIAL REGISTRATION: EudraCT, 2013-004657-24 . Registered on 5 September 2014.

What's past is prologue: Chinese medicine and the treatment of recurrent urinary tract infections.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) has a recorded history of over 2000 years that may be used to authenticate and guide modern treatments for disease, and also identify neglected but potentially useful treatment strategies. However this process is often based on over-simplistic conceptions of tradition and history that fail to take into account the dynamic nature of 'traditions' and underestimate the importance of contextual factors in their interpretation. MATERIALS AND METHODS: As part of a process of defining good practice for a clinical trial of CHM for recurrent urinary tract infections, a selective review of classical Chinese medical texts was undertaken to investigate the historical treatment of urinary diseases specified by the traditional category of Lin diseases. RESULTS: The historical review provided interesting insights into the evolution and meaning of Lin diseases and how pertinent data may be found, precisely, outside the boundaries of the categories on which the original investigation was premised. Although there were interesting parallels and continuities in the classical and modern understandings of the aetiology, pathophysiology and treatment of urinary diseases, there were also important divergences. CONCLUSIONS: It became apparent that, in the search for 'traditional' herbs to treat a particular modern syndrome it is essential to contextualise remedies, including as far as possible the intertextual, social, cultural, and gender context, and conditions of practice. Historical ethnopharmacology adds a level of subtlety and complexity to over-simplistic attempts at bioprospecting. Some insights that emerged from this historical review could inform the proposed clinical trial but these have had to be filtered through the constraints of modern regulatory procedures. Further research is required on how best to integrate the wealth of data that exists in historical texts with the desire to produce effective herbal products for the modern world.

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.

The challenges of treating women with recurrent urinary tract infections in primary care: a qualitative study of GPs' experiences of conventional management and their attitudes towards possible herbal options.

AIM: To explore GPs' experiences of managing recurrent urinary tract infections (RUTIs) and their views on the use of herbal medicines for this condition. BACKGROUND: RUTIs are an important problem commonly managed in primary care. Antibiotic prophylaxis is an effective treatment for acute infections but growing microbial resistance, adverse effects, and the lack of sustained long-term benefits mean that novel treatments are required. There are a number of promising reports of herbal medicines being used to treat RUTIs. METHODS: A total of 15 GPs (seven female; aged 34-59 years; in practice from 3 to 31 years) were purposively sampled and took part in semi-structured face-to-face and telephone interviews. Interviews were digitally recorded, transcribed, and analysed using inductive thematic analysis. Data collection and analysis proceeded iteratively to allow emerging themes to inform subsequent interviews. FINDINGS: Participants were aware of the disabling effect of RUTIs on women's lives. GPs experienced significant challenges in their management of RUTIs with decisions about the provision of antibiotics being particularly complex. While some participants were open to the possibility of herbal treatment options they required more research into effectiveness and safety, better regulation of herbal practitioners, and assurance about herbal quality control and potential herb-drug interactions.

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

BACKGROUND: There 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. METHODS: The 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. RESULTS: Recommendations 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. CONCLUSION: The 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.

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 I(2) 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.

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.

Guidelines for randomised controlled trials investigating Chinese herbal medicine.

UNLABELLED: ETHNOGRAPHIC RELEVANCE: Clinical trials investigating Chinese herbal medicine (CHM) have been frequently criticised for their lack of scientific rigour. As part of the GP-TCM project a team of experienced clinical researchers and CHM practitioners have developed clinical trial guidelines for CHM that combine an appreciation for traditional methods of practice with detailed and practical advice on research methodology. MATERIALS AND METHODS: This paper presents an executive summary of this work. It introduces the practice of CHM and the key considerations that need to be addressed whilst researching this traditional medical system. RESULTS: These guidelines emphasise the importance of identifying best practice, and then developing and applying appropriate and rigorous research methodologies to investigate CHM as a whole system. CONCLUSIONS: It is hoped that this will encourage a thoughtful and meticulous process of investigation that will clarify the contribution that CHM can make to our future healthcare. Innovative new approaches are considered including the application of the new "omic" technologies and systems biology as a way of enhancing our understanding of traditional practice.