Detections of organophosphate and pyrethroid insecticide metabolites in urine and sweat obtained from women during infrared sauna and exercise: A pilot crossover study.

Synthetic pesticides such as organophosphates and pyrethroids are commonly used worldwide yet the metabolic and long-term human health effects of these environmental exposures are unclear. Urinary detections of metabolites involving both classes of insecticides have been documented in various global populations. However, reports documenting similar detections in human sweat are sparse. In this study, the concentrations of four insecticide metabolites were measured using liquid chromatography coupled with tandem mass spectrometry in repeated sweat and urine collections (n = 85) from 10 women undergoing three interventions (control, infrared sauna and indoor bicycling) within a single-blinded randomised crossover trial. The Friedman test with post-hoc two-way analysis of variance, the related-samples Wilcoxon signed rank test and the Spearman's rank-order correlation test were used to analyse the results. Organophosphate metabolites were detected in 84.6% (22/26) and pyrethroids in 26.9% (7/26) of the collected sweat samples (pooled per individual, per intervention). Urinary concentrations of three of the four metabolites marginally increased after infrared sauna bathing: 3,5,6-trichloro-2-pyridinol (z = 2.395, p = 0.017); 3-phenoxybenzoic acid (z = 2.599, p = 0.009); and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid (z = 2.090, p = 0.037). Urinary 3-phenoxybenzoic acid also increased after exercise (z = 2.073, p = 0.038) and demonstrated the most temporal variability (days to weeks) of any of the urinary metabolites. Definitive sweat/urine correlations were not demonstrated. These results indicate metabolites from organophosphate and pyrethroid pesticides can be detected in human sweat and this raises intriguing questions about perspiration and its role in the metabolism and excretion of synthetic pesticides.

Red Light Phototherapy Using Light-Emitting Diodes Inhibits Melanoma Proliferation and Alters Tumor Microenvironments.

Background: Total annual cancer rates have decreased due to improved treatment and prevention. However, the incidence of melanoma is rising, and not all patients respond to immune and targeted approaches. Therefore, we sought to determine the efficacy of red light (RL) phototherapy in preclinical models of melanoma. Methods: Melanoma cells (A375, B16F10, MNT-1) were irradiated with RL. Melanoma proliferation, apoptosis, oxidative stress, and p53 phosphorylation were measured in vitro. In C57BL/6 mice, phototherapy safety, B16F10 tumor growth, and immunocyte infiltration were assessed following RL. Results: In vitro, 640 J/cm2 RL decreased cellular proliferation without increasing apoptosis, while 1280 J/cm2 increased apoptosis. RL increased intracellular reactive oxygen species generation and p53 phosphorylation. In animal models, 2560 J/cm2 RL significantly prevented melanoma growth and increased the expression of CD103+ dendritic cells. 1280 and 1920 J/cm2 RL decreased tumor volume, but not significantly. RL did not cause skin inflammation or erythema in normal skin. Conclusion: RL represents a potentially safe and effective melanoma therapeutic. RL prevented tumor growth and increased the expression of immune markers, such as CD103, that are associated with favorable melanoma outcomes. Further research is needed to determine the optimal clinical treatment regimen for melanoma using RL.

Outcomes in surgical management of sinonasal malignancy-A single comprehensive cancer center experience.

BACKGROUND: Sinonasal malignancies are a complex and diverse group of tumors. Over the past five decades, treatment advances have changed the management paradigms for these tumors. Our aim was to analyze the outcomes of patients from a comprehensive cancer center. MATERIALS AND METHODS: We retrospectively assessed 400 patients with sinonasal malignancies treated with surgery at our center between 1973 and 2015. Multiple variables were reviewed to assess the influence on 5-year outcomes. RESULTS: The median age was 56 years (IQR 46.8-68). Two hundred and fifty-nine (65%) were males and 141 (35%) were females. Overall survival (OS) and disease-specific survival (DSS) improved in the last analyzed decade. Orbital invasion, advanced pT-classification and pN-classification, and melanoma histology were associated with poorer outcomes. CONCLUSION: Treatment outcomes for patients with sinonasal malignancy have improved over time. This is likely multifactorial with advances in surgical technique, adjuvant treatment, and patient selection. pT-classification, pN-classification, orbital invasion, and histology are predictive of survival.

Home-based devices in dermatology: a systematic review of safety and efficacy.

There is increasing demand for home-based devices for the treatment of dermatologic conditions and cosmesis. Commercially available devices include intense pulsed light, laser diodes, radiofrequency, light-emitting diodes, and ultraviolet B phototherapy. The objective of this report is to evaluate the current evidence regarding the efficacy and safety of home-based devices for the treatment of skin conditions. A systematic search of PubMed, Embase, and Cinahl was conducted on November 9, 2020 using PRISMA guidelines. Original research articles that investigated the efficacy and safety of home-based devices for dermatologic use were included. Bibliographies were screened for additional relevant articles. Strength of evidence was graded using the Oxford Centre for Evidence-Based Medicine guidelines. Clinical recommendations were then made based on the quality of the existing literature. After review, 37 clinical trials were included-19 were randomized controlled trials, 16 were case series, and 2 were non-randomized controlled trials. Ultimately, from our analysis, we recommend the home-based use of intense pulsed light for hair removal, laser diodes for androgenic alopecia, low power radiofrequency for rhytides and wrinkles, and light-emitting diodes for acne vulgaris. Trials investigating ultraviolet B phototherapy for psoriasis revealed mixed evidence for home treatments compared to clinic treatments. All devices had favorable safety profiles with few significant adverse events. Limitations to our review include a limited number of randomized controlled trials as well as a lack of data on the long-term efficacy and safety of each device.

Infrared sauna as exercise-mimetic? Physiological responses to infrared sauna vs exercise in healthy women: A randomized controlled crossover trial.

BACKGROUND: Passive heat therapies have been reported to have similar effects on the cardiovascular system as exercise. Studies supporting these findings in healthy populations have predominantly been done with men using warm water immersions or traditional saunas, rather than newer infrared-based saunas. OBJECTIVE: To explore short-term thermal and cardiovascular responses in women using an infrared sauna as compared to moderate-intensity exercise. STUDY DESIGN: Randomized controlled crossover trial with balanced allocations. SETTING: Brisbane, Australia (August 2019 - March 2020) PARTICIPANTS: Ten healthy women (36 ±â€¯9 years) INTERVENTIONS: 45 min of resting, infrared sauna or indoor bicycling PRIMARY OUTCOME MEASURES: tympanic/skin temperatures; respiratory rate; blood pressure; arterial stiffness; heart rate variability RESULTS: Tympanic temperatures were elevated during infrared sauna as compared to both control (mean diff = +1.05 oC ±â€¯SEM 0.12 oC, 95% C.I.: 0.73 - 1.36, p < 0.0005) and exercise (mean diff = +0.79 oC ±â€¯SEM 0.12 oC, 95% C.I.: 0.49 - 1.08, p < 0.0005). Respiratory rates were higher during exercise as compared to both control (mean diff = +7.66 ±â€¯SEM 1.37, 95% C.I.: 4.09 - 11.23, p < 0.0005) and infrared sauna (mean diff = +6.66 ±â€¯SEM 1.33, 95% C.I.: 3.20 - 10.11, p < 0.0005). No significant differences in non-invasive measures of blood pressure, arterial stiffness or heart rate variability were detected between any of the interventions. CONCLUSIONS: These findings suggest the physiological effects of infrared sauna bathing are underpinned by thermoregulatory-induced responses, more so than exercise-mimetic cardiorespiratory or cardiovascular activations.

Microbial Diversity and Characteristics of Kombucha as Revealed by Metagenomic and Physicochemical Analysis.

Kombucha is a fermented tea made from a Symbiotic Culture of Bacteria and Yeast (SCOBY) with a long history of use as a health tonic. It is likely that most health benefits come from the tea and fermentation metabolites from specific microbial communities. Despite its growing importance as a functional health drink, the microbial ecosystem present in kombucha has not been fully documented. To characterize the microbial composition and biochemical properties of 'The Good Brew' original base kombucha, we used metagenomics amplicon (16S rRNA and ITS) sequencing to identify the microbial communities at the taxonomic level. We identified 34 genera with 200 microbial species yet described in kombucha. The dominance of organic acid producing microorganisms Acetobacter, Komagataeibacter and Starmerella are healthy for the human gut and their glucose metabolising activities have a putative role in preventing conditions such as diabetes and obesity. Kombucha contains high protein (3.31 µg/mL), high phenolic content (290.4 mg/100 mL) and low sugars (glucose: 1.87 g/L; sucrose 1.11 g/L; fructose: 0.05 g/L) as compared to green tea. The broad microbial diversity with proven health benefits for the human gut suggests kombucha is a powerful probiotic. These findings are important to improve the commercial value of kombucha and uncover the immense prospects for health benefits.

Disparities and guideline adherence for HPV testing among patients with oropharyngeal squamous cell carcinoma, NCDB, and SEER.

BACKGROUND: Human papilloma virus testing for oropharyngeal squamous-cell carcinoma has been recommended by the National Comprehensive Cancer Network since 2012. We examine disparities, reported rates of human papillomavirus (HPV) testing, and the impact on these findings of limitations with the variable in database registries. METHODS: The HPV variable was queried for patients with oropharyngeal squamous carcinoma (OPSCC) from 2013 to 2016 in National Cancer Data Base (NCDB) and Surveillance, Epidemiology, and End Results (SEER). Multivariable regression was used to identify disparities based on sociodemographic variables. Sensitivity analyses were used to investigate limitations of the variable. RESULTS: Despite limitations in the HPV variable in the databases, there was less than 100% adherence to recommended testing, and there were significant disparities in multiple sociodemographic variables. For example, in NCDB 70% of white versus 60.4% of black patients were tested (odds ratio [OR] 0.75, confidence interval [CI] 0.66-0.85, p ≤ 0.0001); in SEER 59.8% of white and 47.6% of black patients were tested (OR 0.73, CI 0.67-0.81; p ≤ 0.0001). CONCLUSIONS: Disparities exist among patients undergoing testing for HPV-associated OPSCC and adherence to guideline recommended HPV testing has been suboptimal. In addition, the HPV variable definition, especially as it relates to p16 positivity, and use in these two registries should be improved.

Metastatic Cutaneous Squamous Cell Carcinoma Involving the Parotid Gland: Experience Outside of the Sun Belt.

OBJECTIVE: To characterize a subset of patients with metastatic head and neck cutaneous squamous cell carcinoma in a tertiary North American center and describe oncologic outcomes following definitive treatment. STUDY DESIGN: Retrospective chart review. SETTING: National Cancer Institute-designated Comprehensive Cancer Center. METHODS: We conducted a retrospective chart review of patients with cutaneous squamous cell carcinoma with metastases to intraparotid lymph nodes who underwent parotidectomy between 1993 and 2020. Baseline patient and tumor characteristics were assessed. Regional control, disease-specific survival, and overall survival were estimated using Kaplan-Meier method. Multivariate analysis was used to determine the relationship between adverse pathological features and survival. RESULTS: A total of 122 patients were included. The median age was 76, 84.4% of patients were male, and 17.2% were immunosuppressed. Regional control, disease-specific survival, and overall survival were 68.5%, 70.7%, and 59.4% at 5 years, respectively. Perineural and lymphovascular invasion were predictive of worse disease-specific survival. Extracapsular spread was observed in 90.2% of patients and was not a significant predictor of outcome. CONCLUSIONS: We found the demographics and oncologic outcomes of our cohort in the Northeast United States to be comparable with those previously reported in Australia and the Sun Belt of the United States. We noted a high rate of extracapsular spread but did not find it to be a significant predictor of recurrence or survival. Future efforts should address the impact of extracapsular spread on prognosis and adjuvant treatment decisions.

Turning up the heat on COVID-19: heat as a therapeutic intervention.

Enveloped viruses such as SAR-CoV-2 are sensitive to heat and are destroyed by temperatures tolerable to humans. All mammals use fever to deal with infections and heat has been used throughout human history in the form of hot springs, saunas, hammams, steam-rooms, sweat-lodges, steam inhalations, hot mud and poultices to prevent and treat respiratory infections and enhance health and wellbeing. This paper reviews the evidence for using heat to treat and prevent viral infections and discusses potential cellular, physiological and psychological mechanisms of action. In the initial phase of infection, heat applied to the upper airways can support the immune system's first line of defence by supporting muco-ciliary clearance and inhibiting or deactivating virions where they first lodge. This may be further enhanced by the inhalation of steam containing essential oils with anti-viral, mucolytic and anxiolytic properties. Heat applied to the whole body can further support the immune system's second line of defence by mimicking fever and activating innate and acquired immune defences and building physiological resilience. Heat-based treatments also offer psychological benefits and enhanced mental wellness by focusing attention on positive action, enhancing relaxation and sleep, inducing 'forced-mindfulness', and invoking the power of positive thinking and 'remembered wellness'. Heat is a cheap, convenient and widely accessible therapeutic modality and while no clinical protocols exist for using heat to treat COVID-19, protocols that draw from traditional practices and consider contraindications, adverse effects and infection control measures could be developed and implemented rapidly and inexpensively on a wide scale. While there are significant challenges in implementing heat-based therapies during the current pandemic, these therapies present an opportunity to integrate natural medicine, conventional medicine and traditional wellness practices, and support the wellbeing of both patients and medical staff, while building community resilience and reducing the likelihood and impact of future pandemics.

Acute effects of dietary plant nutrients on transcriptome profiles: evidence from human studies.

The health benefits of long-term dietary plant ingestion are well-established. However, literature on acute nutritional challenges is very limited. This study aimed to identify available evidence on transcriptomics responses to acute ingestion of plants or plant extracts and identify signature gene profiles that may serve as biomarkers of health status. We systematically searched electronic databases and extracted information based-on inclusion criteria such as human clinical studies, single plant-based nutrients and outcomes reported on acute transcriptome responses. A total of 11 studies reported on acute intake of plant dietary interventions. Four studies investigating natural oil extracts with three reporting on whole plants and two studies on natural plant-derived extracts. Gene expression was found to be associated with immune response (7 studies), inflammation (9 studies), metabolism (8 studies), cellular processes and cancer. The finding of this systematic review suggests that acute ingestion may significantly impact diverse physiological and pathological pathways including inflammatory, immune, cancer and oxidative stress pathways. Transcriptomics approach is proven to be an effective strategy in discovery of these anticipated mechanisms. Further studies are now required to validate and continue exploring the short-term health impact of dietary plants and their bioactive phytochemicals on gene expression and function.

Novel Oral Anticoagulant Based Versus Vitamin K Antagonist Based Double Therapy Among Stented Patients With Atrial Fibrillation: Insights From the PIONEER AF-PCI Trial.

BACKGROUND: Among stented patients with atrial fibrillation, double therapy with a novel oral anticoagulant plus single antiplatelet therapy (SAPT) reduces bleeding or cardiovascular rehospitalizations compared with a vitamin K antagonist (VKA) based triple therapy regimen. A recent study demonstrated that apixaban based double therapy reduced bleeding compared with VKA based double therapy. However, it remains unknown whether rivaroxaban based double therapy is superior to a VKA based double therapy. METHODS: Patient with stented atrial fibrillation (n=2124) were randomized to 3 groups: rivaroxaban 15 mg od plus a P2Y12 inhibitor (Group 1, n=709); rivaroxaban 2.5 mg bid plus dual antiplatelet therapy (DAPT; Group 2, n=709); and warfarin plus DAPT (Group 3, n=706). Before randomization, subjects were stratified according to a prespecified duration of DAPT (1, 6, or 12 months). After the prespecified DAPT duration, subjects in Group 2 were switched to rivaroxaban 15 mg plus low dose aspirin, and those in Group 3 were switched to VKA plus low dose aspirin. The Wei, Lin, and Weissfeld time to multiple events method was used to compare the occurrence of all bleeding and cardiovascular rehospitalizations among subjects on a novel oral anticoagulant versus VKA based double therapy. RESULTS: A total of 906 subjects were prespecified to a 1 or 6 months DAPT duration and received at least one dose of study drug. Twenty subjects (3.3%) assigned to novel oral anticoagulant+SAPT, and 15 (5.1%) subjects assigned to VKA+SAPT experienced multiple rehospitalizations. In total, 124 (20.3%) events occurred among subjects on novel oral anticoagulant+SAPT compared with 87 (29.6%) among subjects on VKA+SAPT (hazard ratio=0.65 [95% CI, 0.45-0.93], P=0.008). CONCLUSIONS: Among stented patients with atrial fibrillation, rivaroxaban plus SAPT was superior to warfarin plus SAPT in lowering total bleeding and cardiovascular rehospitalization. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01830543.

A hot topic for health: Results of the Global Sauna Survey.

OBJECTIVE: Sauna-bathing is an ancient tradition that is gaining popularity across the world as a wellness tool. There is a growing body of medical evidence supporting the role of saunas, or whole-body thermotherapy, as a form of treatment for a range of health issues. However, the demographics, motivations and experiences of current sauna bathers have not yet been explored on a global scale. This study is designed to explore these themes. DESIGN: An online 71-item questionnaire compiling information on the individual characteristics, sauna-related habits and perceived health and wellness experiences of regular sauna bathers was conducted from October 2016 to October 2017. The validated 'SF-12' quality of life scoring tool was incorporated into the questionnaire to measure physical and mental indicators of well-being. RESULTS: Of 572 logins recorded, 482 valid responses were generated. Both men (51.3%) and women (48.7%) were represented, and respondents were predominantly well-educated (81.8%), non-smoking (90.6%), regularly-exercising (78.8%) individuals of normal-to-overweight status (87.1%) who sauna-bathed approximately 1-2 times per week. The key reasons indicated by respondents for sauna-bathing included relaxation/stress reduction, pain relief and socializing. Nearly a third of respondents reported medical conditions and of this subset, those with back/musculoskeletal pain and mental issues cited the greatest improvements in their conditions with sauna-bathing. Of all respondents, 83.5% reported sleep benefits after sauna use. Analysis of well-being scores after stratifying respondents into three groups by sauna-bathing frequency (group I: <5 times per month; group II: 5-15 times per month; group III: >15 times per month) revealed group II respondents had slightly higher mental well-being scores (Kruskal-Wallis testing: H = 6.603 > ꭔ2 of 5.991, p = 0.0368, df = 2 with post hoc analysis using Mann-Whitney U test: p = 0.016) as compared to respondents who were sauna-bathing less frequently (group I). No respective differences were detected between the physical well-being scores of any of the three groups. Adverse reactions to sauna-bathing were recorded as mostly minor (93.1%), including primarily symptoms of dizziness, dehydration and headache. However, there were two reports (0.3%) of chest pain and eye irritation requiring hospitalization. CONCLUSIONS: This cross-sectional study documents that sauna-bathing participants, particularly those from Finland, Australia and the United States, are motivated to use saunas predominantly for relaxation, reporting health benefits especially around mental well-being and sleep, with relatively few adverse effects. While these results reinforce some of the known health benefits of sauna bathing, they indicate that further research and better dissemination of existing evidence is needed to fully develop the sauna's potential as a therapeutic intervention.

Cost Implications of Anticoagulation Strategies After Percutaneous Coronary Intervention Among Patients With Atrial Fibrillation (A PIONEER-AF PCI Analysis).

The PIONEER AF-PCI trial demonstrated that in atrial fibrillation patients who underwent intracoronary stenting, either rivaroxaban 15 mg daily plus P2Y12 inhibitor monotherapy (Group 1) or 2.5 mg rivaroxaban twice daily plus dual antiplatelet therapy (DAPT) (Group 2) was associated with fewer recurrent hospitalizations, primarily for bleeding and cardiovascular events, compared with standard-of-care vitamin K antagonist and DAPT (Group 3). Associated costs are unknown. This study estimates costs associated with rivaroxaban strategies compared with vitamin K antagonist and DAPT. Medication costs were estimated using wholesale acquisition costs, medication discontinuation rates, and costs of monitoring. Using a large US healthcare claims database, the mean adjusted increase in 1-year cost of care for individuals with atrial fibrillation and percutaneous coronary intervention (PCI) rehospitalized for bleeding, cardiovascular, and other events was compared with those not rehospitalized. Using adjudicated rehospitalization rates from PIONEER AF-PCI, cost differences were estimated. Rates of rehospitalization for bleeding were 6.5%, 5.4%, 10.5%, and 20.3%, 20.3%, 28.4% for cardiovascular events in Groups 1, 2, and 3. Medication and monitoring costs were $3,942, $4,115, and $1,703. One-year costs for all recurrent hospitalization costs and/or patient for the groups were $24,535, $20,205, and $29,756. One-year cost increase associated with bleeding rehospitalizations and/or patient was $4,160, $3,212, and $6,876 and was $13,264, $11,545, and $17,220 for cardiovascular rehospitalizations and/or patient. Overall estimated cost per patient was $28,476, $24,320, and $31,458. Compared with warfarin, both rivaroxaban treatment strategies had higher medication costs, but these were more than accounted for by fewer hospitalizations.

Lifestyles and mindsets of Olympic, Paralympic and world champions: is an integrated approach the key to elite performance?

OBJECTIVES: The holy grail of any nation in the global sporting race is to better understand, replicate and sustain podium winning performances on the world stage. International sporting bodies advocate a holistic approach to the athletic profile and environmental and system-level factors required for world-class sporting performance, yet key lifestyle, relational, training and performance practices are commonly overlooked. We aimed to explore the contribution, interplay, and impact of lifestyle and psychological factors among a sample of world-class, champion athletes. METHODS: Open-ended, semistructured face-to-face interviews were conducted with 10 World, Olympic and Paralympic Champion athletes that covered their sporting development and athletic profile including their mindset, training and competition practices, along with lifestyle and other key factors to which they attributed their success. A thematic approach guided by grounded theory principles, was employed to source and analyse their perspectives and experiences and determine common themes. RESULTS: Four dominant and overlapping themes emerged: psychological attributes, interpersonal relationships, performance strategies and lifestyle practices. All athletes attributed their success to psychological rather than physical factors, and the vast majority relied on mental rehearsal skills and recovery practices. CONCLUSION: The athletic profile and support required to reach and sustain podium-level performance is multidimensional, integrated and individualised and psychological factors are paramount. Championship performance is likely to occur at the intersection of psychological prowess, interpersonal support, effective performance strategies and lifestyle. An integrated approach inclusive of these dimensions can be used to guide athlete development and support at both an individual level and a collective level.

MTHFR isoform carriers. 5-MTHF (5-methyl tetrahydrofolate) vs folic acid: a key to pregnancy outcome: a case series.

PURPOSE: To evaluate the possibility of correcting metabolic defects in gametes and embryos due to methylene tetra hydrofolate reductase (MTHFR) isoforms C677T and A1298C, by supplementation with 5-methyl THF instead of synthetic folic acid. In these couples, high doses of folic acid lead to UMFA (un-metabolized folic acid) syndrome. METHODS: Thirty couples with fertility problems lasting for at least 4 years, such as recurrent fetal loss, premature ovarian insufficiency, or abnormal sperm parameters, with two thirds of them having failed assisted reproductive technology (ART) attempts were included in this program. For all couples, at least one of the partners was a carrier of one of the two main MTHFR isoforms. Most of the women had been previously treated unsuccessfully with high doses of folic acid (5 mg/day), according to what is currently proposed in the literature. The couples carrying one of the isoforms were treated for 4 months with 5-MTHF, at a dose of 600 micrograms per day, before attempting conception or starting another attempt at ART. The duration of treatment corresponding to an entire cycle of spermatogenesis is approximately 74 days. RESULTS: In this first series of 33 couples, one couple was not followed-up, and two are still currently under treatment. No adverse effects were observed. Thirteen of the couples conceived spontaneously, the rest needing ART treatment in order to achieve pregnancy. Only three couples have, so far, not succeeded. CONCLUSION: The conventional use of large doses of folic acid (5 mg/day) has become obsolete. Regular doses of folic acid (100-200 µg) can be tolerated in the general population but should be abandoned in the presence of MTHFR mutations, as the biochemical/genetic background of the patient precludes a correct supply of 5-MTHF, the active compound. A physiological dose of 5-MTHF (800 µg) bypasses the MTHFR block and is suggested to be an effective treatment for these couples. Moreover, it avoids potential adverse effects of the UMFA syndrome, which is suspected of causing immune dysfunction and other adverse pathological effects such as cancer (especially colorectal and prostate).

Total bleeding with rivaroxaban versus warfarin in patients with atrial fibrillation receiving antiplatelet therapy after percutaneous coronary intervention.

Among atrial fibrillation (AF) patients undergoing percutaneous coronary intervention (PCI), rivaroxaban with background antiplatelet therapy significantly reduced the first occurrence of bleeding compared to triple therapy with warfarin. This study hypothesized that total bleeding events, including those beyond the first event, would be reduced with rivaroxaban-based regimens. In the PIONEER AF-PCI trial, 2099 patients in the modified intention-to-treat population were randomized to three groups and followed for 12 months: (1) rivaroxaban 15 mg once daily plus a P2Y12 inhibitor (N = 696); (2) rivaroxaban 2.5 mg twice daily plus dual antiplatelet therapy (DAPT) (N = 706); and (3) dose-adjusted warfarin plus DAPT (N = 697). Descriptive statistics for the number of subjects who experienced one or more bleeding events were calculated. The total number of bleeding events was compared across treatment groups using the Wei, Lin, and Weissfeld method. A total of 514 and 439 events of clinically significant bleeding and bleeding requiring medical attention occurred throughout the study. Compared to triple therapy with warfarin, rivaroxaban-based regimen was associated with a reduction in total events of clinically significant bleeding (Group 1 vs. Group 3: HR 0.64 [95% CI 0.49-0.85], p < 0.001, NNT = 11; Group 2 vs. Group 3: HR 0.62 [95% CI 0.48-0.80], p < 0.001, NNT = 10). Similarly, rivaroxaban reduced the total bleeding events requiring medical attention (Group 1 vs. Group 3: HR 0.66 [95% CI 0.49-0.89], p < 0.001, NNT = 14; Group 2 vs. Group 3: HR 0.64 [95% CI 0.48-0.85], p = 0.002, NNT = 13). Rivaroxaban-based regimen reduced the total bleeding events compared with VKA-based triple therapy in stented AF patients. One clinically significant bleeding event could be prevented with rivaroxaban use for every 10-11 patients treated, and one bleeding requiring medical attention could be prevented with rivaroxaban for every 13-14 patients treated. These data provide evidence that total bleeding events, including those beyond the first event, are reduced with rivaroxaban-based antithrombotic regimens. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT01830543 (PIONEER AF-PCI).

Clinical Effects of Regular Dry Sauna Bathing: A Systematic Review.

INTRODUCTION: Many health benefits are claimed by individuals and facilities promoting sauna bathing; however the medical evidence to support these claims is not well established. This paper aims to systematically review recent research on the effects of repeated dry sauna interventions on human health. METHODS: A systematic search was made of medical databases for studies reporting on the health effects of regular dry sauna bathing on humans from 2000 onwards. Risk of bias was assessed according to the Cochrane Collaboration guidelines. RESULTS: Forty clinical studies involving a total of 3855 participants met the inclusion criteria. Only 13 studies were randomized controlled trials and most studies were small (n < 40). Reported outcome measures were heterogeneous with most studies reporting beneficial health effects. Only one small study (n = 10) reported an adverse health outcome of disrupted male spermatogenesis, demonstrated to be reversible when ceasing sauna activity. CONCLUSIONS: Regular dry sauna bathing has potential health benefits. More data of higher quality is needed on the frequency and extent of adverse side effects. Further study is also needed to determine the optimal frequency and duration of distinct types of sauna bathing for targeted health effects and the specific clinical populations who are most likely to benefit.

Expert clinician's perspectives on environmental medicine and toxicant assessment in clinical practice.

BACKGROUND: Most clinicians feel ill-equipped to assess or educate patients about toxicant exposures, and it is unclear how expert environmental medicine clinicians assess these exposures or treat exposure-related conditions. We aimed to explore expert clinicians' perspectives on their practice of environmental medicine to determine the populations and toxicants that receive the most attention, identify how they deal with toxicant exposures and identify the challenges they face and where they obtain their knowledge. METHODS: A qualitative study involving semi-structured interviews with expert environmental clinicians in Australia and New Zealand was conducted. Interviews were recorded and transcribed, and themes were identified and collated until no new themes emerged. RESULTS: Five dominant themes emerged from 16 interviews: (1) environmental medicine is a divided profession based on type of practice, patient cohort seen and attitudes towards nutrition and exposure sources; (2) clinical assessment of toxicant exposures is challenging; (3) the environmental exposure history is the most important clinical tool; (4) patients with environmental sensitivities are increasing, have unique phenotypes, are complex to treat and rarely regain full health; and (5) educational and clinical resources on environmental medicine are lacking. CONCLUSIONS: Environmental medicine is divided between integrative clinicians and occupational and environmental physicians based on their practice dynamics. All clinicians face challenges in assessing toxicant loads, and an exposure history is seen as the most useful tool. Standardised exposure assessment tools have the potential to significantly advance the clinical practice of environmental medicine and expand its reach across other clinical disciplines.

The health impact of residential retreats: a systematic review.

BACKGROUND: Unhealthy lifestyles are a major factor in the development and exacerbation of many chronic diseases. Improving lifestyles though immersive residential experiences that promote healthy behaviours is a focus of the health retreat industry. This systematic review aims to identify and explore published studies on the health, wellbeing and economic impact of retreat experiences. METHODS: MEDLINE, CINAHL and PsychINFO databases were searched for residential retreat studies in English published prior to February 2017. Studies were included if they were written in English, involved an intervention program in a residential setting of one or more nights, and included before-and-after data related to the health of participants. Studies that did not meet the above criteria or contained only descriptive data from interviews or case studies were excluded. RESULTS: A total of 23 studies including eight randomised controlled trials, six non-randomised controlled trials and nine longitudinal cohort studies met the inclusion criteria. These studies included a total of 2592 participants from diverse geographical and demographic populations and a great heterogeneity of outcome measures, with seven studies examining objective outcomes such as blood pressure or biological makers of disease, and 16 studies examining subjective outcomes that mostly involved self-reported questionnaires on psychological and spiritual measures. All studies reported post-retreat health benefits ranging from immediately after to five-years post-retreat. Study populations varied widely and most studies had small sample sizes, poorly described methodology and little follow-up data, and no studies reported on health economic outcomes or adverse effects, making it difficult to make definite conclusions about specific conditions, safety or return on investment. CONCLUSIONS: Health retreat experiences appear to have health benefits that include benefits for people with chronic diseases such as multiple sclerosis, various cancers, HIV/AIDS, heart conditions and mental health. Future research with larger numbers of subjects and longer follow-up periods are needed to investigate the health impact of different retreat experiences and the clinical populations most likely to benefit. Further studies are also needed to determine the economic benefits of retreat experiences for individuals, as well as for businesses, health insurers and policy makers.