Investigating the association between the symptoms of women with Fibromyalgia, Digestive function, and markers of the microbiota of the Gastrointestinal Tract (The FIDGIT Study): study protocol.

BACKGROUND: Fibromyalgia a common idiopathic condition affecting around 1.4% of adults globally. Its signature symptom is chronic widespread pain, with a constellation of somatic and psychological symptoms. Fibromyalgia is associated with significant reductions in quality of life, yet to date there is no biochemical marker for its diagnosis. Previous studies have indicated a strong association with gastrointestinal dysfunction, and more recently, alterations to the gut microbiome. No studies have examined the inter-relationship between fibromyalgia, gastrointestinal dysfunction, and the microbiome. This prospective observational case-controlled study will gather data on gastrointestinal function, dietary intake, fermentation patterns of ingested carbohydrates, and symptoms commonly associated with fibromyalgia. These will be evaluated alongside human gene expression and metatranscriptomic analysis of the oral and faecal microbiome. METHODS: Adult women aged ≥18 years diagnosed with fibromyalgia and/or meeting ACR 2016 criteria, and healthy family or age-matched controls will be recruited from the community. From consenting participants, we will collect detailed survey information and samples of blood, urine, stool, saliva, and breath. DISCUSSION: This is the first prospective study examining interactions between digestive function, human gene expression, and the gut microbiome together with general, and fibromyalgia-specific, symptoms experienced by New Zealand women. This exploration will allow an in-depth understanding of clinically relevant factors that are associated with fibromyalgia and will guide further research and contribute to improved management of this poorly understood condition. TRIAL REGISTRATION: The study was approved by the New Zealand Health and Disability Committee (HDEC) (ref: 20/CEN/197) and registered with the Australia and New Zealand Clinical Trials Registry (ANZCTR), registration number ACTRN12620001337965. Written consent will be obtained after providing participants with detailed information about the procedures. Access to data will be restricted to the immediate research team, and all samples and survey data will be deidentified and coded before analysis.

Persisting Cancer in Black Salve Treated Skin Lesions: Results of a Large 5 Year Retrospective Analysis of Australian Histopathology Specimens.

BACKGROUND: To date there has been minimal research on the use of black salve escharotics. Whether cancer persistence is a frequent finding in treatment areas, the types of lesion being treated by patients, whether rural patients are more likely to use black salve and whether current government prevention initiatives are succeeding are all issues needing investigation. METHODS: This study was a large national retrospective black salve pathology case series from 2015 to 2019. Five private pathology companies with 1471 collection centers located in 5 of the 8 Australian states and Territories provided de-identified skin pathology report information where black salve treatment had been documented in the pathology request. RESULTS: Over the 5-year period 409 patients had treated 475 lesions with black salve. Benign lesions were present at the treatment site in 18% of cases; persisting cancer was found in 34.2% of the remaining black salve treated areas. The majority of treatment areas were located on the head and neck. Black salve caused necrosis of normal tissue when treating benign lesions, refuting claims of cancer specificity. Likelihood of black salve use increased with rurality based on Modified Monash (MM) scores. Black salve use, despite regulatory efforts, appears to be increasing with specimen numbers more than doubling from 2015 to 2019. CONCLUSIONS: Patients undergoing histopathological assessment of black salve treatment areas have high rates of cancer persistence. Patients are applying black salve to benign lesions and lesions in cosmetically sensitive areas. Rural patients have higher proportional rates of black salve use. The increasing incidence of black salve pathology specimens suggests current Australian black salve public health initiatives are failing.

Understanding of black salve toxicity by multi-compound cytotoxicity assays.

BACKGROUND: Black salve is a controversial complementary and alternative medicine (CAM) associated with skin toxicity and skin cancer treatment failures. Black salve formulations vary between manufacturers and contain a number of botanical and synthetic constituents. The skin cancer cytotoxicity of a number of these constituents has not been assessed to date. The alkaloids from the rhizomes of Sanguinaria canadensis, a key black salve ingredient, have had their single compound cytotoxicity assessed; however, whether they possess synergistic cytotoxicity with other compounds has not been studied and is of direct clinical relevance. This research aimed to improve our understanding of the skin cancer cytotoxicity of black salve constituents. METHODS: The cytotoxicity of individual and combination black salve constituents were assessed against the A375 melanoma and A431 squamous cell carcinoma cell lines. Cytotoxicity was determined using the Resazurin assay with fluorescence measured using a Tecan Infinite 200 Pro Microplate reader, compound cytotoxicity being compared to that of the topical cancer therapeutic agent, 5- fluouracil. Docetaxal was used as a positive control. Dunnetts p value was used to determine whether significant synergistic cytotoxicity was present. RESULTS: Sanguinarine was the most cytotoxic compound tested with a 24-hour IC50 of 2.1 µM against the A375 Melanoma cell line and 3.14 µM against the A431 SCC cell line. All black salve constituents showed greater cytotoxicity against the two skin cancer cell lines tested than the skin cancer therapeutic 5-Fluouracil with 24 hours of compound exposure. Chelerythrine and minor Quaternary Benzophenanthridine Alkaloids (QBAs) present in black salve, at concentrations not having a cytotoxic effect by themselves, boosted the cytotoxic effects of sanguinarine. This could be a synergistic rather than additive cytotoxic effect although the synergistic effect was cell line and concentration dependent. CONCLUSIONS: Black salve contains several cytotoxic compounds, a number of which have been found to possess synergistic cytotoxicity for the first time against skin cancer cell lines. In addition, these compounds together increase the overall cytotoxic effect. Assessing multi-compound cytotoxicity in herbal medicine can provide additional information about both their therapeutic and toxicity potential. As black salve is currently being used by patients, further cytotoxicity work should be undertaken to assess whether synergistic cytotoxicity exists when tested in normal skin cells.

Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate the benefits and risks of zinc formulations compared with controls for prevention or treatment of acute viral respiratory tract infections (RTIs) in adults. METHOD: Seventeen English and Chinese databases were searched in April/May 2020 for randomised controlled trials (RCTs), and from April/May 2020 to August 2020 for SARS-CoV-2 RCTs. Cochrane rapid review methods were applied. Quality appraisals used the Risk of Bias 2.0 and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Twenty-eight RCTs with 5446 participants were identified. None were specific to SARS-CoV-2. Compared with placebo, oral or intranasal zinc prevented 5 RTIs per 100 person-months (95% CI 1 to 8, numbers needed to treat (NNT)=20, moderate-certainty/quality). Sublingual zinc did not prevent clinical colds following human rhinovirus inoculations (relative risk, RR 0.96, 95% CI 0.77 to 1.21, moderate-certainty/quality). On average, symptoms resolved 2 days earlier with sublingual or intranasal zinc compared with placebo (95% CI 0.61 to 3.50, very low-certainty/quality) and 19 more adults per 100 were likely to remain symptomatic on day 7 without zinc (95% CI 2 to 38, NNT=5, low-certainty/quality). There were clinically significant reductions in day 3 symptom severity scores (mean difference, MD -1.20 points, 95% CI -0.66 to -1.74, low-certainty/quality), but not average daily symptom severity scores (standardised MD -0.15, 95% CI -0.43 to 0.13, low-certainty/quality). Non-serious adverse events (AEs) (eg, nausea, mouth/nasal irritation) were higher (RR 1.41, 95% CI 1.17 to 1.69, NNHarm=7, moderate-certainty/quality). Compared with active controls, there were no differences in illness duration or AEs (low-certainty/quality). No serious AEs were reported in the 25 RCTs that monitored them (low-certainty/quality). CONCLUSIONS: In adult populations unlikely to be zinc deficient, there was some evidence suggesting zinc might prevent RTIs symptoms and shorten duration. Non-serious AEs may limit tolerability for some. The comparative efficacy/effectiveness of different zinc formulations and doses were unclear. The GRADE-certainty/quality of the evidence was limited by a high risk of bias, small sample sizes and/or heterogeneity. Further research, including SARS-CoV-2 clinical trials is warranted. PROSPERO REGISTRATION NUMBER: CRD42020182044.

Honeybee products for the treatment and recovery from viral respiratory infections including SARS-COV-2: A rapid systematic review.

BACKGROUND: This rapid review systematically evaluated the effects of honeybee products compared to controls for the prevention, duration, severity, and recovery of acute viral respiratory tract infections (RTIs), including SARS-CoV-2, in adults and children. METHODS: Cochrane rapid review methods were applied. Four English databases plus preprint servers and trial registries were searched for randomized controlled trials (RCTs). The evidence was appraised and synthesized using RoB 2.0 and GRADE. RESULTS: 27 results were derived from 9 RCTs that included 674 adults and 781 children. In hospitalized adults with SARS-CoV-2, propolis plus usual-care compared to usual-care alone reduced the risk of shock, respiratory failure and kidney injury and duration of hospital admission. Honey was less effective than Guaifenesin for reducing cough severity at 60-minutes in adults with non-specific acute viral RTIs. Compared to coffee, honey plus coffee, and honey alone reduced the severity of post-infectious cough in adults. Honey reduced the duration of cough in children compared to placebo and salbutamol; and the global impact of nocturnal cough after one night compared to usual-care alone and pharmaceutical cough medicines. CONCLUSION: More studies are needed to robustly assess honeybee's role in SARS-CoV-2 and non-specific viral respiratory infections. PROTOCOL REGISTRATION: PROSPERO: CRD42020193847.

Hydrogen-methane breath testing results influenced by oral hygiene.

The measurement of hydrogen-methane breath gases is widely used in gastroenterology to evaluate malabsorption syndromes and bacterial overgrowth. Laboratories offering breath testing provide variable guidance regarding oral hygiene practices prior to testing. Given that oral dysbiosis has the potential to cause changes in breath gases, it raises concerns that oral hygiene is not a standard inclusion in current breath testing guidelines. The aim of this study was to determine how a pre-test mouthwash may impact hydrogen-methane breath test results. Participants presenting for breath testing who had elevated baseline gases were given a chlorhexidine mouthwash. If a substantial reduction in expired hydrogen or methane occurred after the mouthwash, breath samples were collected before and after a mouthwash at all breath sample collection points for the duration of testing. Data were evaluated to determine how the mouthwash might influence test results and diagnostic status. In 388 consecutive hydrogen-methane breath tests, modifiable elevations occurred in 24.7%. Administration of a chlorhexidine mouthwash resulted in significantly (p ≤ 0.05) reduced breath hydrogen in 67% and/or methane gas in 93% of those consenting to inclusion. In some cases, this modified the diagnosis. Mean total gas concentrations pre- and post-mouthwash were 221.0 ppm and 152.1 ppm (p < 0.0001) for hydrogen, and 368.9 ppm and 249.8 ppm (p < 0.0001) for methane. Data suggest that a single mouthwash at baseline has a high probability of returning a false positive diagnosis. Variations in gas production due to oral hygiene practices has significant impacts on test interpretation and the subsequent diagnosis. The role of oral dysbiosis in causing gastrointestinal symptoms also demands exploration as it may be an underlying factor in the presenting condition that was the basis for the referral.

Corrigendum to "Choose your shortcuts wisely: COVID-19 rapid reviews of traditional, complementary and integrative medicine" [Integr Med Res 2020; 9: 100484].

[This corrects the article DOI: 10.1016/j.imr.2020.100484.].

A systematic review of the association between fibromyalgia and functional gastrointestinal disorders.

BACKGROUND: Fibromyalgia and functional gastrointestinal disorders (FGID) including irritable bowel syndrome (IBS) are common conditions presenting in clinical settings and are more prevalent in women. While the relationship between IBS and fibromyalgia has been demonstrated, a review of the prevalence of the broader group of FGID in adults with fibromyalgia has not been undertaken. The aim of this review was to systematically review the published literature, identifying the comorbidity of FGID in people with fibromyalgia, and to discuss the clinical implications, limitations of current research and areas of interest for future research. METHODS: Medline, Embase, CINAHL and Web of Science were searched during June 2019. Results were screened for original research articles meeting established criteria for identification of FGID in adults diagnosed with fibromyalgia. RESULTS: A total of 14 studies involving 1340 adults with fibromyalgia, 363 healthy controls and 441 adults with other pathologies were included in this review. Only 1 of the 14 studies included surveyed the full range of FGID . Functional gut disorders were matched to Rome II criteria for reporting and comparison. In addition to increased abdominal pain and functional bloating or gas, IBS of mixed-pattern and constipation-types appear to be more prevalent than diarrhoea-predominant IBS in adults with fibromyalgia. CONCLUSION: This review confirms previous reports that IBS is common in people living with fibromyalgia and suggests that IBS-mixed and constipation types predominate. An association with a range of FGID other than IBS is suggested, but data are limited. Research exploring the association between fibromyalgia and functional gastrointestinal dysfunction beyond IBS are warranted.

Zinc for the prevention and treatment of SARS-CoV-2 and other acute viral respiratory infections: a rapid review.

BACKGROUND: The global COVID-19 pandemic has prompted an urgent search for interventions to prevent and treat SARS-CoV-2. Higher risk of infection and adverse outcomes coincide with populations with chronic diseases and elderly who are at risk of zinc deficiency. Through several mechanisms zinc may prevent, reduce severity and duration of symptoms. METHOD: An a priori protocol was registered with PROSPERO on 27th April 2020 (CRD42020182044). Eight databases (one Chinese) and four clinical trial registries (one Chinese) were searched for randomised and quasi-randomised controlled trials (RCTs), evaluating single or adjunct zinc against placebo or active controls, for prevention and/or treatment of SARS-CoV-2, other coronaviruses or related infections. RR constraints included not searching bibliographies or contacting authors, single reviewers with calibration and second reviewer checking, meta-analyses and quality appraisal of critical and study primary outcomes only and reporting results as they became available. RESULTS: 118 publications of 1,627 records met the inclusion criteria (35 Chinese and 83 English publications), 32 for prevention, 78 for treatment and 8 for both. Four RCTs specific to SARS-CoV-2 are ongoing; two are investigating zinc for prevention and two for treatment. As of 7 July 2020, no results were available. A wide range of zinc forms, including nasal spray/gel, lozenges, liquid, tablets and intramuscular were investigated. CONCLUSION: Currently, indirect evidence suggests zinc may potentially reduce the risk, duration and severity of SARS-CoV-2 infections, particularly for populations at risk of zinc deficiency including people with chronic disease co-morbidities and older adults. Direct evidence to determine if zinc is effective for either prevention or treatment of SARS-CoV-2 is pending. In the interim, assessing zinc status of people with chronic diseases and older adults, as part of a SARS-CoV-2 clinical work-up, is reasonable as both groups have a higher risk of zinc deficiency/insufficiency and poorer outcomes from SARS-CoV-2.