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Introduction Urinary kryptopyrroles (UKP), or the ‘Mauve factor’, was first described in the early 1960s with an observed association with psychiatric illness. Since this time, there has been growing interest in the clinical importance of UKP testing for a range of clinical conditions. However, there are substantive gaps in the available evidence to inform appropriate application and interpretation of UKP tests. With this in mind, this study describes the observed health conditions, treatments and diagnostic application of UKP by clinicians using it within their clinical practice. Methods Observational cross-sectional self-report online survey of Australian clinicians, recruited through a company that provides functional testing (including UKP analysis), who identify as having used UKP testing within their clinical practice. The survey collected data on participant demography and characteristics of their clinical practice, their approach to the diagnosis and interventions used to clinically manage elevated UKP (eUKP), and the observed clinical importance of eUKP for a range of health conditions. Results The survey was completed by 86 respondents. The majority of participants used nutritional supplements (76.7%), dietary therapy (60.5%) and lifestyle changes (58.1%) to clinically manage eUKP. Nervous system (86.0%) and gastrointestinal (64.0%) conditions were most commonly observed by respondents to be linked to eUKP. Anxiety was observed by 91.9% of respondents to be associated with eUKP and was also the condition most commonly described as markedly improving following treatment of eUKP. A number of factors were reported to be associated with eUKP by the majority of respondents including mood swings (100%), social withdrawal (92.5%), compulsive behaviour (82.4%) and emotional eating (77.8%). Implications Given the substantive gaps in evidence associated with UKP testing, this data may provide direction for researchers to design projects that reflect UKP testing as it is used in grass-roots clinical practice.

Objectives The aim of this literature review is to examine the relationship between Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and assisted reproductive technologies in men and women accessing fertility services. Design Systematic literature review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses Methods This systematic literature review involved searches conducted through the Medline, EMBASE, CINAHL and Scopus databases to identify observational studies examining MTHFR polymorphism incidence in infertile couples seeking support through In vitro fertilisation and/or Fertility clinics. Results The included studies (n = 16) identified an association with male infertility including azoospermia, oligozoospermia and teratozoospermia for the Methylenetetrahydrofolate reductase polymorphisms C677T and A1298C. A newly-identified AA allele of the MTHFR G1793A polymorphism was found to be protective against oligospermia and males with this polymorphisms had higher sperm counts. Studies also associated the new allele MTHFR179GA GG allele with female infertility. A strong association between individuals with C677T homozygous alleles receiving assisted reproductive technology and higher AMH levels, implantation failure, and lower ovarian responsiveness was also reported. Women with A1298C polymorphisms had few follicles, lower E2 levels and were less likely to have a viable pregnancy or live birth after in vitro fertilisation. Implantation failed in one in four embryos that were homozygous for C677T. Conclusions The MTHFR genetic polymorphism may be associated with infertility in couples seeking assisted reproductive technologies.

This notice clarifies that at no point during and up to the time of publication of this article was JB offering commercial nutrition consultations for mental health. This was a role taken up subsequently to the article's publication. JB did advertise free consultations in a student nutrition clinic several years prior to the preparation of the article, and skin/dermal therapy and lifestyle coaching consultations, though this was not deemed to constitute a valid conflict of interest when making such declarations upon the article's submission. We would also like to declare that JS works as a consulting Naturopath in private practice.

Background: Fibromyalgia (FMS) is a complex condition that is characterized by various pain syndromes and fatigue, among other symptoms experienced. Current medical treatment of FMS involves both p...

Objective To assess how the introduction of the Generalized Anxiety Disorder-7 (GAD-7) was utilised in consultations by students in complementary medicine undergraduate teaching clinic throughout Australia. This study also aims to evaluate the reported severity of anxiety in patients attending the clinic, the practitioner type consulted, and the treatment prescribed by the Complementary Medicine (CM) students for patients with anxiety during 2017-18. Design This is a longitudinal, observational study using data from the Endeavour Wellnation clinics across Australia. Methods Patients anxiety levels were measured with the GAD-7 at consultations with student practitioners during 2017–2018. Patients that completed the GAD-7 more than once had their subsequent GAD-7 scores compared to assess changes in outcome score. Information was taken from SurveyGizmo for patients who visited the student clinic making it a sub-group analysis. Results Three hundred and ninety (n = 390) GAD-7 surveys were completed from the 50, 896 consultations that occurred in 2017 and 2018 (0.7 % of consultations). Most patients (29.7 %, n = 116) reported moderate anxiety on several days. Thirty-nine patients (n = 39) completed the GAD-7 more than once. Nutrition patients were the most frequent to complete the GAD-7 more than once. Conclusions The introduction of the GAD-7 at Australian complementary medicine teaching clinics reported usage frequency of 0.7 % of consultations in the first two years. The reason for this usage frequency may be due to low encouragement of the use of Patient Reported Outcome Measurements (PROMs) by clinic supervisors and in pre-clinic subjects, students having low confidence in the use of the GAD-7 or other PROMs or lack of understanding of their benefits by either the student practitioner or the client. The lack of subsequent GAD-7 use in follow-up consultations may be contributing to a decreased substantiation of treatment outcomes for both the patient and the students. Consideration of more frequent use of the GAD-7 in regular clinical practice to enhance clinical outcomes and practitioner education is warranted.

Cannabis medicines are in demand from the public for treating a range of diseases and symptoms; however, clinicians are reluctant to prescribe these products because of limited evidence and prescribing information. To generate this evidence, quality clinical trials of cannabis medicines must be undertaken, yet their design is a complex, often uncharted territory, and involves the cooperation and sharing of knowledge of multiple stakeholders. Before designing a clinical trial, researchers require a clear understanding of the potential therapeutic benefit cannabis medicines may have, the form and formulation of the product, and the dose to be investigated. Researchers must also be aware of the applicable pharmaceutical regulations in the country or jurisdiction where the research is to be undertaken, as well as manufacturing or licensing regulations that may be imposed at the source of the cannabis product. Importantly, collaborations with industry are a key to the successful outcome of cannabis medicines clinical trials. Without funding and sponsorship of clinical trials, the ability to generate quality data will be limited and the evidence for cannabis medicines to be registered as therapeutics lacking. Collaborations between researchers, industry, and regulators, working together in sharing knowledge, are therefore critical to generate high quality cannabis medicines research.

Objectives: The specific aims are: 1) To characterize the health, wellness, and lifestyle of graduate and undergraduate students, and how these characteristics change over time; 2) To evaluate associations between lifestyle factors and gut microbiota populations and diversity; and 3) To evaluate associations between stress and stress management practices with sleep habits, quality of life, and overall health. Design: The International Cohort on Lifestyle Determinants of Health (INCLD Health) longitudinal cohort study is designed to assess health behaviors and lifestyle practices amongst adults studying complementary and integrative health (CIH) and higher-education students more generally after at least one to six years of exposure to CIH education. INCLD Health will adhere to the Strengthening the Reporting of Observational studies in Epidemiology (STROBE) guidelines. Settings/Location: Colleges and universities with a CIH focus or interest with the flagship site being the National University of Natural Medicine. Participants: Adults currently enrolled in a college or university with a CIH focus or interest. Outcome Measures: Study visits will be conducted at baseline, 6 months, then every 12 months until the end of each participants' degree program. Measures include anthropometrics; serum and salivary biomarkers of cardiovascular risk, reproductive hormones, and cortisol; nutritional intake measured by a digital food frequency questionnaire; sequencing of fecal microbiota; plus validated questionnaires investigating mood, perceived stress, stress management practices, physical activity, sleep, and wellness. Conclusions: The INCLD Health Study, approved by the NUNM IRB in late 2018, will enroll a unique cohort of adults to characterize the use of CIH practices in relation to short- and long-term health. Our study design provides a breadth of information that could be implemented at multiple sites internationally allowing for comparisons across diverse student cohorts with relatively low cost and personnel.

BackgroundThe paucity of empirical research examining complementary medicine (CM) use in palliative care in France compared with other countries results in a gap in scientific knowledge. This study aims to describe the frequency and the cause of palliative care patients consulting with a CM clinician along with the conventional physicians.MethodsThis study is an observational cross-sectional survey conducted in three palliative care centres in Lyon, France, between July 2017 and May 2018: two tertiary hospitals and one palliative care unit in a private hospital. Inpatients and outpatients visiting the palliative care clinics with a primary diagnosis of cancer were invited to participate in the study. Using a 19-item paper-based survey instrument, we collected data on the participants’ personal characteristics, health service utilisation and attitudes towards CM.ResultsFrom the 138 participants meeting the inclusion criteria, 100 (72.4%) were included in the study. On average, they were 62.9 years old (SD 12.4) and the majority were women (60%). The primary cancer site was mostly colorectal (29.0%), breast (15.0%) and gynaecological (11.0%). The most commonly visited CM clinician was the aromatherapist (72.7%), recording more than six consultations (78.1%) for symptom management (21.9%). Visits to an osteopath were reported by 28.6% of patients, and 45.8% of osteopathy users reported visiting an osteopath more than six times for symptom management (62.5%). Participants visiting a naturopath (15.3%) reported less than four visits and indicated symptom management as the most common reason (76.9%).ConclusionsOur findings show a substantial proportion of palliative care patients visit CM clinicians and primarily seek symptom management from CM clinical care.

Depression is a mood disorder which currently affects 350 million individuals worldwide. Recently, research has suggested a protective role of diet for depression. The Mediterranean-style dietary pattern has been highlighted in several systematic reviews as a promising candidate for reducing depressive symptoms. It has been speculated that this could be due to the high polyphenol content of foods commonly found in the diet. Therefore, the aim of this review was to assess the effects of polyphenols found in a Mediterranean diet on the symptoms of depression. A systematic literature review was conducted of original research which assessed the role of polyphenols on the symptoms of depression in humans. The following databases were searched: PROQUEST, SCOPUS (Elsevier), MEDLINE (EBSCO), CINAHL, and EMBase, up to 18 February, 2019. The inclusion criteria consisted of both observational and experimental research in adults aged 18-80 y that assessed depression scores in relation to polyphenol intake. A total of 37 studies out of 12,084 met the full inclusion criteria. Of these, 17 were experimental studies and 20 were observational studies. Several different polyphenols were assessed including those from tea, coffee, citrus, nuts, soy, grapes, legumes, and spices. Twenty-nine of the studies found a statistically significant effect of polyphenols for depression. This review has found both an association between polyphenol consumption and depression risk, as well as evidence suggesting polyphenols can effectively alleviate depressive symptoms. The review uncovered gaps in the literature regarding the role of polyphenols for depressive symptoms in both young adults and men. This review was registered at www.crd.york.ac.uk/PROSPERO as CRD42019125747.

The authors regret that the following information was published incorrectly. The errors that need to be corrected are as follows: 1 The primary outcome of improvements of participants over two months (8 weeks) was 61.7% not 41.7%.2 Fig. 1: Consort diagram was not published.3 Fig. 2: Changes in urinary urgency from baseline to week8 (p = 0.002) was not published4 Fig. 3: Changes in soiled underwear from baseline to week 8 was not published.5 The name of the product is Urox® Junior not Urox® Bedtime Buddy.The authors would like to apologise for any inconvenience caused.

BACKGROUND: Depression is a common mental health condition that affects 1 in 8 males each year, especially young adults. Young adulthood offers an opportunity for early dietary interventions, with research suggesting that a Mediterranean diet (MD) could be beneficial in treating depression. OBJECTIVES: This study aimed to determine if an MD can improve depressive symptoms in young males with clinical depression. METHODS: A 12-wk, parallel-group, open-label, randomized controlled trial was conducted to assess the effect of an MD intervention in the treatment of moderate to severe depression in young males (18-25 y). Befriending therapy was chosen for the control group. Assessments were taken at baseline, week 6, and week 12. MD adherence was measured with the Mediterranean Diet Adherence Score (MEDAS). The primary outcome measure was the Beck Depression Inventory Scale-version II (BDI-II) and secondary outcome was quality of life (QoL). RESULTS: A total of 72 participants completed the study. After 12 wk, the MEDAS scores were significantly higher in the MD group compared with the befriending group (mean difference: 7.8; 95% CI: 7.23, 8.37; P

Myelodysplastic syndrome (MDS) evolves due to genomic instability, dysregulated signalling pathway and overproduction of inflammatory markers. Reactive oxygen species contribute to the inflammatory response, which causes gene damage, cellular remodelling and fibrosis. MDS can be a debilitating condition, and management options in patients with MDS aim to improve cytopenias, delay disease progression, and enhance quality of life. High serum ferritin levels, a source of iron for reactive oxygen species production, correlate with a higher risk of progression to acute myeloid leukaemia, and iron overload is compounded by blood transfusions given to improve anaemia. 6-shogaol is a natural phenolic compound formed when ginger is exposed to heat and/or acidic conditions, and it has been shown to possess anti-tumour activity against leukaemia cell lines and antioxidant effects. This narrative review assessed the potential benefits of this phytochemical in lower-risk MDS patients through examining the current evidence on the pharmacological and therapeutic properties of ginger and 6-shogaol.

Palliative care for cancer deals with physical, psychosocial, and spiritual issues faced by cancer patients, their families, communities, and healthcare providers. Research on complementary medicine (CM) use in France is limited despite high rates of reported CM use in other countries including by palliative patients. This study describes the use of CM by individuals receiving palliative care in Lyon, France. This study employed an observational cross-sectional survey design. The study was conducted in three palliative care centers in Lyon, France; two tertiary hospitals and one palliative care unit (3 sites). Inpatients and outpatients visiting the palliative care clinic with a primary diagnosis of cancer at each study site were invited to participate. Of 138 eligible patients, 100 completed the survey (RR 72.4%). The majority (90.7%) reported using CM in the previous 6 months or since their primary cancer diagnosis. Participant CM use was either the same (20.7%) or increased since their primary cancer diagnosis (33.7%). Average out-of-pocket expenses associated with CM use in the previous 6 months or since diagnosis were €157.40 (SD €330.15). The most common CM health professional visited was an aromatherapist (72.7%), a Coupeurs de feu (38.6%), osteopath (28.6%) and naturopath (15.3%). The most common CM used were aromatherapy oils (33.7%), homeopathy (30.0%), and vitamins (29.4%). This second survey on CM use in France; is the first conducted in palliative care centers. Results show people with cancer in Lyon, France, have a very high prevalence of CM utilization.

Objectives Excluding gluten containing foods from the diet is medically indicated for the management of coeliac disease, wheat allergy, gluten ataxia, non-coeliac gluten sensitivity, and dermatitis herpetiformis. However, the number of people following a gluten free diet (GF diet) far exceeds the number of people with an indication for such dietary restriction. It has been suggested that 70% of individuals who are recommended GF diets by complementary medicine practitioners have not had coeliac disease adequately excluded. The aim of this study was to describe the diagnostic and clinical management practices of naturopaths, Western herbalists and nutritionists (non-dietetic) associated with recommending GF diets. Design, subjects and outcome measures A cross-sectional 40-item questionnaire was developed and administered online to 145 Australian naturopaths, nutritionists (non-dietetic) or Western herbal medicine practitioners via professional associations and a practice based network (PRACI) between February and April 2017. Demographic data and practice information related to recommending GF diets was collected. Results A total of 56.5% (82/145) practitioners reported that in the majority of cases they did not undertake any recommended diagnostic process, and 48% (71/145) of practitioners referred to a general practitioner to exclude medical conditions related to gluten ingestion prior to recommending a GF diet. A total of 10% (15/145) ordered coeliac serology through local laboratories, and 17% (24/145) through functional pathology companies. Non-coeliac gluten sensitivity was diagnosed by 56% (82/145) through an elimination and reintroduction diet, and 61% (88/145) used a diet and symptom diary. IgG antibody tests were used by 23% (33/145) of practitioners, and 5% (7/145) used kinesiology prior to recommending a GF diet. Conclusion Clinical guidelines for the diagnosis of gluten related disorders are not followed by a substantial number of complementary medicine practitioners prior to recommending a GF diet. Strategies are required to improve the standard of practice in this area.

Introduction Urinary kryptopyrroles (UKP) are described as pyrrole compounds excreted in urine and have been associated with a broad range of signs and symptoms. However, causality between elevated UKP and the described symptoms of pyrrole disorder have not been established. A four stage project has been developed to verify the validity of a urinary kryptopyrroles test and attempt to establish a reference range for a healthy population. Methods Stage one will consist of a survey to clinicians who are currently using UKP testing in their practice to understand their perceptions of the clinical value and applicability of the test in addition to identifying the condition for stage three. Stage two consists of a clinical trial to establish a normal reference range for UKP in a healthy population. Stage three is a clinical trial exploring the correlation, if any, between UKP in a diagnosed health condition to the healthy population group. Stage four is a pragmatic trial assessing UKP levels in patients as used by clinicians as part of routine clinical practice. Recruitment Recruitment for stage one will be via email invitation to SAFE Analytical laboratories Pty Ltd customer database. Stage two and three will be targeting the wider community in the greater Brisbane area in Queensland and aims to recruit 120 participants per stage. Recruitment for stage four will be conducted through community based clinical practices. Conclusion At the conclusion of all stage, the validation of the UKP test from SAFE Analytical laboratories will be analysed. Formulation of a reference range for a healthy population range will be explored and compared to a diagnosed condition and other conditions as tested by clinicians in practice.

© Copyright 2019, Mary Ann Liebert, Inc., publishers 2019. Objectives: This study aims to explore the treatment interventions complementary and integrative medicine (CIM) practitioners use in the management of an emerging health condition, increased intestinal permeability (IP), and the association these methods have on the observed time to resolve this condition. Design and setting: A cross-sectional survey of Australian naturopaths, nutritionists, and Western herbal medicine practitioners was undertaken (n = 227) through the Practitioner Research and Collaboration Initiative (PRACI) network. Outcome measures: Frequencies and percentages of the treatment methods, including chi-square analysis to examine the associations between treatment methods and observed time to resolve IP. Results: Thirty-six CIM practitioners responded to the survey (response rate 15.9%). CIM practitioners were found to use a multimodal approach in the management of IP with 92.6% of respondents using three or more categories of treatment interventions (nutritional, herbal, dietary, and lifestyle) with a mean total of 43.0 ± 24.89 single treatment interventions frequently prescribed. The main treatments prescribed in the management of IP were zinc (85.2%), probiotics: multistrain (77.8%), vitamin D (75.0%), glutamine (73.1%), Curcuma longa (73.1%), and Saccharomyces boulardii (70.4%). CIM practitioners also advocate patients with IP to reduce alcohol (96.3%), gluten (85.2%), and dairy (75.0%) consumption. Evaluation of antibiotics (75.0%) and nonsteroidal anti-inflammatory drugs (73.1%) prescriptions were frequently advised by CIM practitioners. A longer observed time to resolve IP was seen in CIM practitioners who did not reduce intense exercise in the management of IP (p = 0.02). Conclusions: This study represents the first survey of the treatments prescribed by CIM practitioners for IP and suggests that CIM practitioners use numerous integrative treatment methods for the management of IP. The treatment interventions frequently prescribed by CIM practitioners align with preclinical research, suggesting that CIM practitioners prescribe in accordance with the published literature. The findings of this study contribute to the implementation of clinical research in the management of IP, which considers multiple concurrent treatments.

Introduction A gluten free diet (GFD) is indicated for the medical management of coeliac disease as well as gluten ataxia, dermatitis herpetiformis, and wheat allergy. Complementary medicine practitioners (CMPs) recommend removing gluten from the diet, but it is not known what symptoms or conditions they recommend gluten free diets for. The aim of this study is to describe for what conditions Australian naturopaths, Western herbalists and nutritionists (non-dietetic) recommend a gluten free diet. Methods This was a sub-group analysis nested within a cross-sectional survey of practitioners recruited through the PRACI practice-based research network and relevant professional associations. A 40-item survey collected information on sociodemographic characteristics, practice and professional characteristics and specific questions on gluten related disorders between February and August 2017. Data was described using frequencies and percentages along with one-way ANOVA to determine group differences. Results One hundred and forty-five complementary practitioners responded to the survey. The gastrointestinal conditions most frequently prescribed a GFD for were non-coeliac gluten sensitivity (99%), medically diagnosed coeliac disease (95.2%), inflammatory bowel disease (73.1%) and irritable bowel syndrome (60%). The most frequently prescribed GFDs for extra-intestinal conditions were skin conditions (60%), children with developmental disorders (53.1%), mental health conditions (46.2%) and weight management. Discussion Results suggest that given the broad application of GFDs by CMPs, there may be therapeutic benefits for conditions other than known gluten related disorders. However, in the absence of appropriate investigations for gluten related disorders, the recommendation and positive response to a GFD may be inadvertently treating an undiagnosed gluten related disorder. In addition, a GFD may also be inadvertently managing other unknown intolerances that require different clinical management. Conclusion This research highlights the need for further investigation into the potential benefits resulting from prescribing GFDs for conditions where there is no established evidence for the exclusion of dietary gluten.

© 2018 Elsevier Ltd Background & aims: Folate supplements are commonly prescribed by health professionals for a number of different conditions, however, the absorption of the different derivatives remains unclear. This pilot trial aims to assess the absorption of various forms of folate supplements in a healthy population. Methods: A four-week, single blinded, randomised control trial was conducted on 30 healthy individuals. The intervention included supplementation with 500mcg of either folic acid, folinic acid or 5-Methyltetrahydrofolate (5-MTHF). Fifteen participants were allocated to the intervention and fifteen to the control group for comparison. At baseline (week 0) a case report was completed and pathology tests for serum folate, B12 and MTHFR polymorphisms were conducted. Follow up serum folate blood pathology tests were assessed at week 2 and week 4 along with additional food diaries. Results: Of the cohort, 87% (n = 26) were found to have a MTHFR polymorphism with both A1298C (n = 12) and C677 T (n = 18) being tested. Only13% (n = 4) of participants had no mutation. The different MTHFR mutations were observed across both the control group and all of the intervention groups. The mean (±SD) baseline folate was 33.7 nmol/L ± 7.55 (Reference range: >9.0). Participants who had both A1298C and C677 T polymorphism had lower baseline folate with a mean (±SD) of 29 nmol/L ± 8.75. During the four weeks an overall increase in mean serum folate was observed in both the folinic acid and 5-MTHF group. The folinic acid intervention saw a mean (±SD) increase of 15.3 nmol/L ± 3.56 and 5-MTHF saw a mean (±SD) increase of 9.1 nmol/L ± 1.67, however a decrease in mean serum folate was detected in the folic acid group. In the folinic acid and 5-MTHF groups, serum folate increases were observed in individuals irrespective of their MTHFR status. Conclusions: This research has provided a foundation for further work investigating folate absorption. The results of the trial suggest that folinic acid has the best absorption, however, it may not have the best bioavailability. More research is required for greater clarification regarding the absorption and bioavailability of these supplements.

Objective Increased intestinal permeability (IP) may play an important role in health and disease. The purpose of this review is to explore the association between IP and diseases frequently found within clinical practice. Design and methods A systematic literature search was conducted up until July 2018 in MEDLINE, PubMed, EMBASE and AMED. A total of 48 articles met the inclusion/exclusion criteria. Results IP is strongly associated with autoimmune disease and liver conditions, with the estimated prevalence of 25–87.5% and 17–65% respectively. IP also correlates with diabetes (30–65%), food allergies/hypersensitivity, irritable bowel syndrome (35.6%), polycystic ovary syndrome and autism (36.7%). Disease severity in addition to clinical symptoms of menstrual disorders, food allergy or hypersensitivity directly correlates with IP. Finally, the severity of IP appears to be exacerbated by the presence of dysbiosis, inflammation and glucose metabolism disorders. Conclusions IP is a potentially influential factor that coincides with a variety of health conditions and diseases. IP should be considered as a factor in the pathophysiology and differential diagnosis for patient’s presenting with autoimmune diseases, non-alcoholic fatty liver disease, liver cirrhosis, polycystic ovary syndrome, irritable bowel syndrome, diabetes, autism, food allergies and food hypersensitivity. Further research is required to determine if IP plays a pathogenic role in the progression and development of disease or whether the disease causes IP. While the clinical significance between IP and these diseases is unclear, the findings of the review suggest the treatment of IP in patients presenting with these conditions may warrant the consideration of clinicians.

ObjectivesNaturopathy is a traditional medicine system informed by codified philosophies and principles, and an emphasis on non-pharmacologic therapeutic interventions. While naturopathy is practiced by approximately 75 000 to 100 000 naturopathic practitioners in at least 98 countries, little is known about the international prevalence of history of consultation with a naturopathic practitioner. This study reports a systematic review and meta-analysis of studies describing the global prevalence of history of consultation with a naturopathic practitioner by the general population.SettingThe included literature was identified through a systematic search of eight databases between September and October 2019, as well as the grey literature.ParticipantsStudies were included if they reported the prevalence rate of consultations with a naturopathic practitioner by the general populationInterventionsSurvey items needed to report consultations with a naturopathic practitioner as defined in the country where data was collected, and not combine naturopathic consultations with other health services or only report consulations for illness populations.Primary and secondary outcome measuresPrimary measures used for the analysis was consultations in the previous 12-months. Other prevalence timeframes were reported as secondary measures.MethodsMeta-analysis of prevalence data was conducted using random effects models based on individual countries and World Health Organisation (WHO) world regions.ResultsThe literature search identified eight manuscripts summarizing 13 studies reporting prevalence for inclusion in the review. All included studies had a low risk of bias. Meta-analysis of the included studies by world region found the 12-month prevalence of history of naturopathy consultations ranged from 1% in the Region of the Americas to 6% in the European and Western Pacific Regions.ConclusionsThere are up to 6-fold differences in the prevalence of naturopathy consults over 12-months between and within world regions, which may be driven by a range of policy, legislative and social factors.Strengths andLimitations of this studyNaturopathy is one of the most commonly used traditional and complementary medicines in the Western world and this is the first systematic review and meta-analysis reporting the prevalence of consutations with a naturopathic practitioner.This study includes only includes data published after 2010 to ensure the results are contemporary, however this may have excluded some studies in countries with older data.The results are limited by the poor availability of data reporting consultations with a naturopathic practitioner, including in countries where a large number of naturopathic practitioners are known to provide care.

Background Nocturnal enuresis or ‘bedwetting’, is a form of night-time urinary incontinence occurring in younger children. A diagnosis can be socially disruptive and psychologically stressful for a child. The most common strategies used by parents are waking the child during the night to use the bathroom and limiting the child's water intake before going to bed. Hypothesis/Purpose To determine if a herbal capsule formulation taken once daily can reduce incidence and frequency of nocturnal enuresis in children. Study Design This randomised double-blind placebo-controlled trial evaluated the efficacy of an herbal medicine product to reduce the symptoms of nocturnal enuresis. Participants, aged between 6 and 14 years of age, were recruited from the community in Australia. They were randomised via computerised random-number generation at study enrolment to receive one or two oral capsules in the morning of either Urox® (Bedtime Buddy®) or placebo. The Paediatric Quality of life (Pin-Q) was used as a quality-of-life measure and waking wet, fluid intake and urinary urgency per week were monitored. Results Forty-one children completed the trial with an attrition rate of 16%. There were more males (64.6%) compared to females (35.4%) and the mean age was 8.6 years. Forty-one point seven percentages (41.7%) of participants had improvements in bed wetting by two months which was a highly clinically relevant effect (Cohen's D = 0.98). The primary outcome found that there was a statistically significant reduction in NE (p = 0.034; CI 0.086–2.095) and between groups using longitudinal analysis (p = 0.04, Coefficient -1.12, CI 95% -2.20 - -0.04). In the secondary outcomes, urinary urgency reduced statistically significantly for the intervention (p = 0.002; a reduction of 18.3% difference for Bedtime Buddy compared to an increase of 3.7% for the placebo). Conclusion Urox® (Bedtime Buddy®) may assist children in reducing nocturnal enuresis compared to placebo. In addition, it may assist in reducing daily incontinence and urinary urgency.

Background Naturopathy, recognised by the World Health Organisation as a European traditional medicine system, is practiced in every world region. Patients in countries where naturopathy is practiced visit a naturopathic practitioner for a range of health concerns including maternal and reproductive health; recognised as a global health priority area. This study aims to examine the characteristics of patients visiting naturopathic practitioners for their maternal and reproductive health concerns, and the clinical care provided by naturopathic practitioners to those patients. Methods An international cross-sectional survey of typical naturopathic practices and their associated patients, conducted in naturopathic clinics in 14 countries and 4 world regions. Naturopathic practitioners(n = 54) were invited to prospectively complete an online survey for up to 20 consecutive cases within the study period. Univariate relationships were examined through chi-square tests. Backwards stepwise logistic regression was employed to explore the characteristics most likely to be associated with individuals visiting a naturopath for maternal and reproductive health. Results Naturopathic practitioners provided data for 852 patients, with 43 (5.0%) visiting a naturopath for maternal and reproductive health concerns such as fertility (54.8%), pregnancy (26.2%), preconception health (11.9%), and lactation, breastfeeding or other postnatal care (7.1%). The regression analysis indicates the practitioners are more likely to prescribe acupuncture (OR 2.71, p Conclusions Individuals are accessing naturopathic practitioners for maternal and reproductive health. An examination of the motivations influencing this population to access naturopathic care and the outcomes of this care is urgently needed. Key messages Naturopathic practitioners throughout the world are being visited for assistance with maternal and reproductive health issues including fertility, pregnancy, preconception and postnatal care. Naturopathic practitioners are prescribing acupuncture, as well as a wide range of other treatments, for maternal and reproductive health issues.

Current evidence suggests that N-Acetyl Cysteine (NAC) administration may help improve outcomes in people with acute respiratory distress syndrome and acute lung injury - conditions that closely resemble the signs and symptoms of COVID-19. Few mild and transient adverse events were reported in published randomised-controlled trials, indicating that NAC may be reasonably safe. These findings suggest that NAC may complement the management of COVID-19 infection, particularly when administered intravenously within an intensive care unit (ICU) environment. Verdict Current evidence suggests that N-Acetyl Cysteine (NAC) administration may help improve outcomes in people with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) - conditions that closely resemble the signs and symptoms of COVID-19. In this rapid review, NAC was predominately administered intravenously to patients with ARDS or ALI, who were at risk of or requiring mechanical ventilation, and were admitted to a hospital intensive care unit. Findings indicated that NAC administration may assist in improving markers of inflammation or oxidation, systemic oxygenation, the need for / duration of ventilation, rate of patient recovery and clinical improvement score. The effects of NAC on patient length of stay, CT/x-ray images, mortality rate and pulmonary complications were inconclusive. Few mild and transient adverse events were noted, indicating that NAC may be safe for use in acute respiratory distress syndrome or acute lung injury. Based on the evidence identified, and the similar symptomatic profiles of ARDS/ALI and COVID-19, the findings suggest that NAC may be used to complement the management of COVID-19 infection within an acute care setting. The safety and efficacy of orally administered NAC for the management of milder forms of COVID-19 infection within the community setting, remains uncertain. The current research evidence suggests NAC warrants further research for acute respiratory viral infections, including COVID-19.

Brief overview Current evidence from published systematic reviews indicate that oral intake of vitamin C may assist with symptoms of acute viral respiratory infections (ARI) by reducing fever and chills, relieving chest pain and assist in reducing symptoms of common cold-induced asthma. Intravenous (IV) vitamin C administration may reduce the need for vasopressor support and the duration of mechanical ventilations in critically ill patients in hospital. COVID-19 has similar signs and symptoms of ARI. Further studies involving patients with COVID-19, either through administration of oral vitamin C in mild cases or IV vitamin C in critical cases, would be advantageous to examine if it is safe and efficacious. Verdict Oral vitamin C may assist with the symptoms of acute respiratory viral infections (ARI) and common cold-induced asthma but no studies have been identified justifying oral vitamin C for the prevention or treatment of coronavirus infections including COVID-19. When taken at onset of ARI, oral vitamin C may reduce the duration of symptoms including fever, chest pain, chills and bodily aches and pains. It may also reduce the incidence of hospital admission and duration of hospital stays. For individuals admitted to hospital with community-acquired pneumonia, vitamin C may improve respiratory function in more severe cases. No major adverse events nor interactions were reported by either method of administration. However, there is an absence of high quality, contemporary clinical research examining this topic. Current evidence suggests further studies are needed to better understand the value of both oral and IV vitamin C for ARI, including COVID-19.

Brief Overview Seven human clinical trials with some risk of bias suggest that multivitamins may be a safe and effective intervention to relieve some symptoms of respiratory tract infections, increase micronutrient status and immune function; however, further research is needed. There is currently insufficient evidence to recommend multivitamins as a therapy for the treatment or prevention of COVID-19. Verdict The overall quality of research examining the effect of prophylactic multivitamin supplementation on the effects of the acute respiratory tract infections (ARTI) is weak. Most of the available research included adults aged 50 years or over recruited through either the community or institutional settings (i.e. hospital facility, residential care facility). The multivitamin supplements used contained at least five vitamins and minerals and were administered between three months and two years (median: 15 months). Based on the available evidence, multivitamin supplementation does not appear to reduce the incidence of ARTI or mortality (both ARTI-related and all-cause). The effect of multivitamins taken before infection on the duration of ARTI is unclear due to conflicting results across studies. Multivitamins may, however, reduce the symptoms associated with ARTI such as headache, conjunctivitis, and activity restriction but not the overall symptom scores. No differences in health service visits, inclusive of primary and tertiary care, has been identified for individuals taking a multivitamin prior to an ARTI.

Background: Naturopathy is one of seven distinct traditional medical systems acknowledged by the World Health Organization. Naturopathic principles and philosophies encourage a focus on multiple body systems during case-taking and the design of treatments. Little is known about whether such teaching translates into practice. This study aimed to characterise naturopathic practice as it relates to the identification of multiple physiological systems in the diagnosis and treatment of patients. Methods: A cross sectional study was conducted in collaboration with the World Naturopathic Federation. A survey capturing clinical diagnostic and treatment considerations for up to 20 consecutive patients was administered to naturopaths in 14 countries. Results: Naturopaths (n = 56) were mostly female (62.5%), aged between 36 and 45 years (37.5%), in practice for 5–10 years (44.6%), and consulting between 11 and 20 patients per week (35.7%). Participants completed the survey for 851 patient cases. Naturopaths reported a greater number of physiological systems relevant to clinical cases where the patients were working age (18–65 years) (IRR 1.3, p = .042), elderly (65 years and over) (IRR 1.4, p = .046), or considered by the naturopath to have a chronic health condition (IRR 1.2, p = .003). The digestive system was weakly associated with patients based on chronicity of the health complaint (V = .1149, p = .004), or having a musculoskeletal complaint (V = .1067, p = .002) autoimmune pathophysiology (V = .1681, p

Background This study aims to explore the conditions complementary and integrative medicine (CIM) practitioners associate with increased intestinal permeability (IP) and the methods they employ to assess IP. Methods A cross-sectional survey of naturopaths, nutritionists and Western herbal medicine practitioners was undertaken (n = 227) through the Practitioner Research and Collaboration Initiative (PRACI) network. Results CIM practitioners (n = 36, response rate 15.9%) associate IP with gastrointestinal (100.0%), autoimmune (91.7%), skin (91.7%), neurological (80.6%), respiratory (55.6%) and liver-related conditions (44.4%). CIM practitioners frequently treat IP (72.7%); observing a minimum 3 months of treatment is required to resolve IP. Patient's signs and symptoms were the main reasons CIM practitioners suspected IP (94.1%). Conclusion CIM practitioners observe a clinical link between IP and a wide range of conditions, including those not yet recognised within the literature. The clinical experience of CIM practitioners holds substantial value to the advancement of research and the clinical management of IP.

Introduction Two of the three pillars of evidence-based practice emphasise the importance of using the best available academic research and experience from clinical practice to inform patient care. This paper aims to outline the potential value of exploring and describing insights from clinical practice through health services research to inform whole system research. Methods Concepts and ideas were developed from non-systematic review of published literature and extensive academic and clinical experience within the disciplines of health services research and clinical trials. Results Through deductive reasoning, complementary and integrative medicine (CIM) practitioners may have identified new understanding of the management of disease not yet seen in published literature. The area where investigating CIM practitioners in clinical practice may advance the clinical understanding of particular conditions is extensive. For instance, increased intestinal permeability (IP) is speculated to be involved in diseases frequently seen within clinical practice. IP is considered multifactorial with involvement from genetic and environmental factors. Conclusions CIM practitioners report clinical experience in the management of digestive disorders; their practice wisdom may add new knowledge to the significance of IP within clinical practice and outline testing parameters. Furthermore, the whole system treatment approach used by CIM practitioners may provide insight into new options for the management of IP not known or shared in published literature. Investigating the approaches CIM practitioners use within clinical practice may provide advancements in the clinical understanding of IP and other conditions. Exploring clinical practice may identify new knowledge that may translate to improvement in patient care.

Ovarian cancer has the lowest survival rate in gynaecologic malignancies with a 5-year survival rate of 43%. Platinum resistance is one of the main drivers of ovarian cancer mortality, of which aberrant methylation has been cited as a significant contributor. Understanding the essential role of the methylenetetrahydrofolate reductase enzyme (MTHFR) on DNA synthesis and repair, and how nutrient status can vastly affect its performance, led to the investigation of MTHFR status and dietary influence on platinum response in epithelial ovarian cancer (EOC) patients. Twenty-five adult female patients who completed first-line platinum-based chemotherapy for primary ovarian cancer were selected from Icon Cancer Centres in Australia. Participants were grouped based on platinum response. A full medical and family history, food frequency questionnaire and single blood test were completed, testing for MTHFR polymorphisms, serum folate, serum and active B12 and homocysteine levels. Nineteen of twenty-five participants had an MTHFR polymorphism. Of those, 20% were compound heterozygous, 12% were heterozygous C677T (CT), 4% homozygous C677T, 12% homozygous A1298C and 28% were heterozygous A1298C (AC). Statistically significant associations were found between dietary zinc (p = 0.0086, 0.0030, 0.0189) and B12 intakes in CT genotypes (p = 0.0157, 0.0068) indicating that zinc or vitamin B12 intakes below RDI were associated with this genotype. There were strong associations of vitamin B6 intakes in AC genotypes (p = 0.0597, 0.0547, 0.0610), and dietary folate in compound heterozygotes with sensitive and partially sensitive disease (p = 0.0627, 0.0510). There were also significant associations between serum folate (p = 0.0478) and dietary B12 (p = 0.0350) intakes above RDI and platinum sensitivity in wild-types as well as strong associations with homocysteine levels (p = 0.0886) and zinc intake (p = 0.0514). Associations with dietary B12 (p = 0.0514) and zinc intakes (p = 0.0731) were also strong in resistant wild types. Results indicate that dietary zinc, B12 and B6 intakes may be associated with platinum sensitivity dependent on MTHFR genotype. These results require further research to clarify the dosages necessary to elicit a response, however, they provide a novel foundation for acknowledging the role of diet on treatment response in EOC.

Background: Glioblastoma (GBM) remains incurable. Patients seek complementary treatments when standard treatments are ineffective, or when cancer symptoms are uncontrolled. Cannabis has intense interest as both therapy and palliation for GBM, but little prospective controlled data exists. We studied the safety and tolerability of two different quality-assured medicinal cannabis preparations in patients with GBM, taking standard treatments. Patients and Methods: Patients with recurrent high-grade glioma (anaplastic astrocytoma or GBM) with no history of substance abuse enrolled in a single-centre phase II double-blind randomized clinical trial comparing two preparations of medicinal cannabis (tetrahydrocannabinol (THC) to cannabidiol (CBD), THC 1:1 CBD and THC 4:1 CBD) taken once daily at night. Retrospective historically matched controls were audited from clinical records as comparators. Results: Patient self-referral for screening was overwhelming (n=921). Both preparations were well tolerated. Side effects included dry mouth, tiredness at night, dizziness, drowsiness, and impaired motor coordination, but no serious adverse events were attributable to the intervention. Sleep was reported as improved from baseline in both groups (95% CI 2.4-2.77; p=0.009). Overall quality of life (FACT-Br) was improved from baseline in both groups with the 1:1 preparation favouring both physical (95% CI 6.49-7.92; p=0.025) and functional (95% CI 15-16.9; p=0.014) capacity. Disease control appeared no worse than historical controls; only 10% of patients experienced progressive disease during the study period, and median overall survival was 11 months. Conclusion: A single nightly dose of medicinal cannabis was safe, well tolerated and appeared to improve sleep, functional wellbeing and quality of life (QOL) compared to baseline, with no negative impact on disease control. The 1:1 preparation is favoured for future studies in people with high-grade brain cancer. Trial Registration: The trial protocol was registered with the Australian New Zealand Clinical Trial Registry (ANZCTR): ACTRN12617001287325. Funding Statement: The funding body, Bioceuticals Pty Ltd, had no involvement with the protocol development, implementation of the trial, collection nor analysis of the trial. The trial was conducted by an independent research institution, Endeavour College of Natural Health which was the initial sponsor for the trial which has now been transferred to Southern Cross University (SCU) due to the lead researcher transferring universities. The funding body paid fees directly to Endeavour and SCU for the trial and supplied the investigational products for the trial in kind Declaration of Interests: All investigators declare no conflict of interest with this study. Prof Charlie Teo and Dr Mike Sughrue are shareholders and founders of Omniscient neurotechnologies for brain tumours but does not conflict with this study. Ethics Approval Statement: The trial was approved by human research ethical committees (HREC), South Eastern Sydney Local Health District HREC: 18/028, University of Technology Sydney HREC: ETH 18-2761 and Endeavour College of Natural Medicine HREC: 20180821.

The following sections are included: Introduction Africa The Americas South Asia Europe Western Pacific Future Prospects Conclusion References