Search

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.

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.

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.

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.

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.

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.

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.

Objective: Neurological complications such as chemotherapy-induced peripheral neuropathy (CIPN) and neuropathic pain are frequent side effects of neurotoxic chemotherapy agents. An increasing survival rate and frequent administration of adjuvant chemotherapy treatments involving neurotoxic agents makes it imperative that accurate diagnosis, prevention, and treatment of these neurological complications be implemented. Methods: A consideration was undertaken of the current options regarding protective and treatment interventions for patients undergoing chemotherapy with neurotoxic chemotherapy agent or experience with CIPN. Current knowledge on the mechanism of action has also been identified. The following databases PubMed, the Cochrane Library, Science Direct, Scopus, EMBASE, MEDLINE, CINAHL, CNKI, and Google Scholar were searched for relevant article retrieval. Results: A range of pharmaceutical, nutraceutical, and herbal medicine treatments were identified that either showed efficacy or had some evidence of efficacy. Duloxetine was the most effective pharmaceutical agent for the treatment of CIPN. Vitamin E demonstrated potential for the prevention of cisplatin-IPN. Intravenous glutathione for oxaliplatin, Vitamin B6 for both oxaliplatin and cisplatin, and omega 3 fatty acids for paclitaxel have shown protection for CIPN. Acetyl-L-carnitine may provide some relief as a treatment option. Acupuncture may be of benefit for some patients and Gosha-jinki-gan may be of benefit for protection from adverse effects of oxaliplatin induced peripheral neuropathy. Conclusions: Clinicians and researchers acknowledge that there are numerous challenges involved in understanding, preventing, and treating peripheral neuropathy caused by chemotherapeutic agents. New insights into mechanisms of action from chemotherapy agents may facilitate the development of novel preventative and treatment options, thereby enabling medical staff to better support patients by reducing this debilitating side effect.

Design A multi-site randomised clinical trial. Participants The Women's Healthy Eating and Living (WHEL) study of patients with breast cancer. Data was collected from 2413 women with breast cancer but without diabetes mellitus, aged 27–70 years at diagnosis. A total of 2064 participants (85.5%) were Caucasian with 1335 (55.3%) college educated. Intervention Dietary analysis including timing of consumption at baseline, year 1 and year 4. A 24-h dietary recall collected by telephone on random days during a 3-week period, stratified for weekends vs weekdays. Nightly fasting duration was estimated by calculating the elapsed hours between the first and last eating episode for each day and subtracting that time from 24h. Potential confounders were identified including daily intake (kilocalories), eating episodes per day and eating after 8pm. Comparator No comparator was used in this study. Major outcomes Participants reported a mean (SD) nightly fasting duration of 12.5h and 4.4 eating episodes per day. One-third of the sample consumed 25kcal or more after 8pm. A short nightly fasting duration ( A short nightly fast ( Each 2-h increase in nightly fasting duration was statistically significant for lower HbA1c level (0.37mmol/mol lower) and more hours of sleep per night. Nightly fasting was not associated with BMI or CRP concentrations. Eating after 8pm was significantly associated with increased higher CRP and BMI. Settings The United States of America: Clinical sites included University of California, San Diego; University of California, Davis; Stanford University; Kaiser Permanente, Northern California; M.D. Anderson Cancer Centre; Arizona Cancer Centre; and Kaiser Permanente Center for Health Research. Conclusion Prolonged nightly fasting duration (13h or more), may be a simple, non-pharmacologic strategy for reducing the risk of breast cancer recurrence. In addition, improvements in gluco-regulation and sleep may be mechanisms of action linked with nightly fasting and breast cancer prognosis.

Corrigendum to “Nutraceuticals and chemotherapy induced peripheral neuropathy (CIPN): A systematic review” [Clin Nutr 32/6 (2013) 888e893] Janet M. Schloss , Maree Colosimo a, , Caroline Airey , Paul P. Masci , Anthony W. Linnane , Luis Vitetta a, * a The University of Queensland, School of Medicine, Centre for Integrative Clinical and Molecular Medicine, Level 5, TRI, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, Brisbane 4102, Australia b Medical Oncology Group of Australia, Clinical Oncology Society of Australia, Queensland Clinical Oncology Group, Brisbane 4000, Australia c Neurology Fellow at Queensland Health, Department of Neurology, Ned Hanlon Building, RBWH, Herston, Brisbane 4006, Australia