Undesirable Symptoms Research Articles

Clinical assessment of the anti-cancer activity of the capsaicin-containing habanero pepper extract in dogs: a preliminary study

The aim of the study was a preliminary assessment of the anti-cancer efficacy of the capsaicin-containing habanero pepper extract in dogs. The study was conducted on a group of 50 dogs (33 females, and 17 males aged 6–18 years) diagnosed with different tumours, and 20 dogs (12 females and 8 males, aged 2-12 years) forming a control group. All animals were administered with a diet supplement based on habanero pepper extract containing capsaicin. Observations were conducted for a period of 6 months, during which time the general condition of the animals administered with the extract was monitored, and haematological as well as biochemical examinations were conducted at 2-week intervals in order to assess the tolerance of the animals to the extract. In the animals of the test group, tumour sizes were measured at monthly intervals. After the end of observations, the tumours were removed and subjected to histopathological tests. As a result of habanero pepper extract administration, the tumour size decreased by 5–50% in 15 dogs, the tumours size remained unchanged in 29 dogs, whereas tumour size increased by 10–30% in 5 animals despite the administration of the extract. The extract was well tolerated by the animals. Temporary undesirable symptoms in the form of vomiting or diarrhoea and licking of the anal region, which could stem from its administration, were observed in only nine dogs of the test group and 5 of the control group. An increase in asparagine aminotransferase (AST) activity was observed in 13 dogs of the test group, alanine aminotransferase (ALT) activity was elevated in 11 dogs, whereas alkaline phosphatase (ALP) increased its activity in 18 dogs. Increases in total bilirubin, urea and creatinine concentration were noted in the serum of 10, 9 and 9 dogs respectively. In the control group, the AST activity increased in 7 dogs, ALT in 5, ALP in 5, and total bilirubin concentration in 6. The preliminary clinical observations indicate that the capsaicin-containing habanero pepper extract exhibits favourable effects on different tumours in dogs and is well tolerated by the animals, thus the obtained results are a good sign for future studies on alternative medications used in dog oncology.

Coumestrol Down-Regulates Melanin Production in Melan-a Murine Melanocytes through Degradation of Tyrosinase.

Pigmentation reflects skin darkening caused by melanin production, but excessive melanin synthesis may cause problems, such as melasma, solar lentigo, dark spots, and freckles. Considerable effort has been devoted to alleviating these undesired symptoms through the development of safe and effective depigmenting agents. Coumestrol, a plant-derived natural isoflavone with an estrogen-like structure and actions, is known to have anti-aging ability, but its potential depigmenting efficacy has not been evaluated. In the present study, we investigated the effects of coumestrol on melanin synthesis in normal melan-a murine melanocytes. Coumestrol significantly reduced melanin synthesis in a concentration-dependent manner up to a concentration of 25 µM without causing cytotoxicity. It also brightened tissue in an artificial skin model (MelanoDerm) that incorporates both human keratinocytes and melanocytes. Interestingly, although coumestrol did not inhibit tyrosinase activity or transcript level in melan-a cells, it clearly decreased the expression level of tyrosinase protein at a concentration of 25 µM. This coumestrol-induced reduction in tyrosinase protein levels was prevented by pretreatment with the proteasome inhibitor MG-132 or the lysosomal proteolysis inhibitor chloroquine. Collectively, our findings indicate that coumestrol exerts an inhibitory effect on melanin synthesis in melan-a cells, at least in part, through degradation of tyrosinase. These findings suggest that coumestrol is a good candidate for use in depigmentary reagents from a cosmetic and clinical perspective.

Comparison of visual function and patient satisfaction with AcrySof ReSTORSN6AD1 multifocal intraocular compared to monofocal intraocular lenses 5

Aim. To compare visual function and satisfaction in patients after implantation of AcrySof ReSTOR SN6AD1 multifocal intraocular lens (IOL), AcrySof SA60AТ spherical monofocal IOL, or Akreos АО aspheric monofocal IOL during cataract surgery.
 Materials. Overall, 34 patients received SN6AD1 multifocal (group 1, 48 eyes), 19 patients received Akreos АО monofocal aspheric (group 2, 30 eyes), and 13 patients received AcrySof SA60AТ monofocal spherical (group 3, 18 eyes) IOL. Patients with multifocal IOL were closely matched for age, sex, and ocular findings with patients who had monofocal IOL implantation. Six months postoperatively, uncorrected/corrected distance visual acuity (UDVA/CDVA), uncorrected intermediate (60 cm) and near (35 cm) visual acuity (UNVA), defocus curve, contrast sensitivity, and a quality-of-life questionnaire were evaluated. Furthermore, independence from glasses and presence of optical phenomena were assessed.
 Results. Patients in group 2 had statistically significant increase in UDVA than that in group 1 (p = 0.037). There was no significant difference in the mean uncorrected intermediate and best corrected distance visual acuities between the groups. UNVA was better in group 1 than that in groups 2 and 3 (p 0.0001). Photopic contrast sensitivity for high spatial frequencies was better in groups 2 and 3. Glare was reported in 5.9% of patients in group 1. Halos occurred in 32.4% of patients in group 1. No one reported undesirable visual symptoms in groups 2 and 3.
 Conclusion. Multifocal IOLs provided higher spectacle independence and satisfactory functional vision over a broad range of distances but were associated with increased subjective visual symptoms and reduced photopic contrast sensitivity for high spatial frequencies and distance visual quality compared with monofocal IOLs.

The Gene as Natural Nanomaterial for Treatment of Diseases

As an application of the grand unified theory (GUT) to medicine, this paper introduces two natural nanomaterials—the gene and electromagnetic wave. They are involved in the proposed treatment of genetic and infectious diseases. It introduces the superstring as the fundamental building block of matter and the basic constituent of dark matter, one of the two fundamental states of matter. It also introduces the primum, unit of visible or ordinary matter, the other fundamental state of matter. They are convertible to each other by the action of basic cosmic or electromagnetic waves. Eleven biological laws define biology as a biological and physical theory. The gene is the primitive ingredient of living things and, therefore, the beginning of biological life and the virus the simplest living thing. Treatment ranges from genetic modification and alteration to remove undesirable symptom through genetic sterilization to stop the spread of the disease and outright destruction of the disease. Genetic sterilization and outright destruction apply also to infectious diseases. The paper concludes with a blueprint for research and development of appropriate technologies for the treatment.

Effect of basal insulin dosage on blood glucose concentration in ambulatory surgery patients with type 2 diabetes

Study objectiveAmong patients with type 2 diabetes treated with insulin, perioperative hyperglycemia and hypoglycemia may cause undesirable symptoms, surgery delay or cancellation, or unexpected hospitalization. Our objective was to compare preoperative glargine dosing regimens on perioperative glycemic control in patients undergoing ambulatory surgery. DesignObservational study. SettingPre- and postoperative holding areas. PatientsOne hundred fifty patients with type 2 diabetes using a once daily, evening insulin glargine regimen undergoing ambulatory surgery were included. InterventionsNone. MeasurementsTo conduct the analysis, patients were divided into four groups based on the percentage of normal evening glargine dose taken. Group 1 took no glargine. Group 2 took 33%-57%. Group 3 took 60%-87% and Group 4 took 100% of their normal dose. The primary outcome was the proportion of patients in each group with blood glucose in the target range (100-180 mg/dL), and the incidence of hypoglycemia (defined as BG <70 mg/dL or symptomatic, requiring glucose). Main resultsGroup 3 had the highest proportion (78%) of patients within target range (P<.001) and Group 4 had the highest proportion of patients with hypoglycemia (P=.01). Patients in Group 3 were significantly more likely to achieve target blood glucose than patients in either Group 1 (P=.001) or Group 4 (P=.002). ConclusionsOur study shows that the percent of normal insulin dose given the evening before surgery directly impacts perioperative glucose levels in ambulatory surgery patients. Patients taking 60%-87% of their usual dose the evening before surgery were likely to arrive in target blood glucose range with decreased risk for hypoglycemia. The mean and mode dose taken in Group 3 were 73% and 75%, respectively, suggesting that the optimal dose may be 75% of normal dose.

Arthroscopic-assisted Acromioclavicular and Coracoclavicular Ligaments Reconstruction for Chronic Acromioclavicular Dislocations: Surgical Technique.

Chronic acromioclavicular (AC) instability is a rare posttraumatic shoulder condition that can lead to undesirable symptoms like persistent pain, muscle fatigue, loss of strength, or even scapular dyskinesis. It is well known that in these cases the superior functional results depend on the restoration of the anatomy and stability of the AC joint in both vertical and horizontal planes. Considering the ligaments degeneration and atrophy in chronic AC joint dislocations, we present an arthroscopic-assisted reconstruction of both the coracoclavicular and AC ligaments using autograft augmentation. In details the coracoclavicular ligaments component is reconstructed using the Tightrope suspension device augmented with a palmaris longus autograft and by the nonanatomic coracoacromial ligament transfer (modified Weaver-Dunn). The AC part is restored by suturing the remainder palmaris longus autograft on the acromion and on the deltotrapezial fascia. Using the construct provided by this technique all the possible ruptured ligaments are reconstructed, optimizing the vertical and horizontal stability of the area, and promising excellent long-term radiologic and functional results.

Abstract 1802: ER-positive breast cancer prevention with the use of hormone replacement therapy

Abstract Menopause occurs in women between the ages of 45 and 55 and often results in undesirable vasomotor symptoms. Hormone replacement therapy (HRT) alleviates these symptoms, including hot flashes, difficulty sleeping, fatigue, and vaginal atrophy. HRT also prevents osteoporosis. PremPro, a currently available HRT formulation that combines conjugated equine estrogens (CE) with medroxyprogesterone acetate, increases the risk of breast cancer. Due to the perceived risk based largely on the results of the Women's Health Initiative (WHI) trial, the number of women taking HRT has decreased dramatically. Duavee, a new form of HRT that combines CE and bazedoxifene (BZA), a selective estrogen receptor modulator (SERM) and degrader (SERD), has recently been approved by the FDA for treatment of moderate to severe hot flashes and to reduce the risk of osteoporosis. Importantly, this CE/BZA mixture not only relieves symptoms associated with menopause, but it also does not stimulate the breast or uterus. Although several preclinical studies suggest that CE/BZA might be protective in the breast, the mechanism of action of this new combination therapy is not known. Our goal, therefore, is to elucidate the underlying molecular mechanisms by which CE/BZA differentially affects estrogen receptor alpha (ERα) action in the mammary gland, using transcriptome and whole genome occupancy analysis in breast cancer cell lines. We are also studying the effects of CE/BZA on early mammary cancer progression in the polyoma middle T antigen (PyMT) transgenic mouse model, which has been shown to be sensitive to estrogens. In addition, we are studying the effects in an ERα-positive patient-derived xenograft mouse model. We have determined that CE modulates gene expression in MCF7 cells similar to 17β-estradiol (E2), and that BZA is able to inhibit these effects. We have also observed that CE increases ERα occupancy versus E2 at response elements associated with some estrogen target genes, whereas CE/BZA decreases this occupancy. In the PyMT mouse model, we have determined that CE/BZA significantly delays the onset of mammary tumors in ovariectomized mice and prolongs their survival when compared to E2 and CE treatment alone. An improved understanding of the molecular mechanisms of CE/BZA action in hormone sensitive breast cancer cell and animal models should have important implications for women considering HRT. Citation Format: Anna G. Dembo, Geoffrey L. Greene. ER-positive breast cancer prevention with the use of hormone replacement therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1802.

Improved Endothelial Function of Endothelial Cell Monolayer on the Soft Polyelectrolyte Multilayer Film with Matrix-Bound Vascular Endothelial Growth Factor.

Endothelialization on the vascular implants is of great importance for prevention of undesired postimplantation symptoms. However, endothelial dysfunction of regenerated endothelial cell (EC) monolayer has been frequently observed, leading to severe complications, such as neointimal hyperplasia, late thrombosis, and neoatherosclerosis. It has significantly impeded long-term success of the therapy. So far, very little attention has been paid on endothelial function of EC monolayer. Bioinspired by the microenvironment of the endothelium in a blood vessel, this study described a soft polyelectrolyte multilayer film (PEM) through layer-by-layer assembly of poly(l-lysine) (PLL) and hyaluronan (HA). The (PLL/HA) PEM was chemically cross-linked and further incorporated with vascular endothelial growth factor. It demonstrated that this approach could promote EC adhesion and proliferation, further inducing formation of EC monolayer. Further, improved endothelial function of the EC monolayer was achieved as shown with the tighter integrity, higher production of nitric oxide, and expression level of endothelial function related genes, compared to EC monolayers on traditional substrates with high stiffness (e.g., glass, tissue culture polystyrene, and stainless steel). Our findings highlighted the influence of substrate stiffness on endothelial function of EC monolayer, giving a new strategy in the surface design of vascular implants.

Analysis of potential drug interactions and adverse reactions to nonsteroidal anti-inflammatory drugs among the elderly

Abstract Objective: The aim of the present study was to analyze potential drug interactions and adverse reactions to NSAIDs in elderly users of a private drug distribution service. Method: A prospective, exploratory and descriptive study with a quantitative approach was performed. The elderly users of NSAIDs attended by the service were interviewed and their prescriptions analyzed between May and September, 2014. Analysis of drug interactions was performed through computerized databases. The post-sales analysis of adverse reactions was performed using the Adverse Drug Reaction Probability Scale. Statistical analysis was performed with the Chi-squared and Fisher's Exact tests. Results: The study evaluated 200 elderly persons, among whom women predominated (56.5%). The average age was 65 years ±10. The NSAIDs accounted for 38.7% of prescription drugs used, and included dipyrone (26.9%), nimesulide (22.8%) and ketoprofen (16.3%). A total of 8.5% of such drugs were considered inappropriate medications for the elderly. A total of 104 potential drug interactions were identified, of which 24% were considered highly clinically significant. The NSAIDs with the greatest risk of interactions were ketoprofen 46.2%, ketorolac 14.4%, nimesulide 12.5% and diclofenac 9.6%. In post-sales monitoring 30.5% of the elderly persons reported undesirable symptoms after the use of NSAIDs, with stomach discomfort the most prevalent (17%). Conclusion: The present study confirmed the importance of monitoring the use of NSAIDs among the elderly due to the increased risk of drug interactions and adverse reactions associated with age, concomitant diseases, multi- prescriptions and polypharmacy. The choice of appropriate drugs for the elderly, the reconciliation of all the medications taken by the patient, and effective pharmaceutical care are measures that can contribute to the rational and safe use of NSAIDs.

The Microbiome and Cancer: Implications for Oncology Nursing Science.

Approximately 1.6 million Americans were diagnosed with cancer in 2014. To combat their disease, many individuals received either curative or palliative treatments that produced undesired symptoms. These symptoms, which often cause significant distress for individuals coping with cancer, may share biologic underpinnings such as epigenetic changes and immune dysregulation. Alterations in the normal flora of the gut may also influence cancer symptoms. The aim of this review is to describe the emerging role for the gut microbiome in cancer research, especially the potential relationship between the gut microbiome and cancer symptoms. Extant literature was reviewed and synthesized. The majority of studies linking the gut microbiota and cancer are animal models and focus on the relationship between dysbiosis and colorectal cancer. Emerging evidence supports that the "gut-brain" connection is a plausible mechanism for "psychoneurological" cancer symptoms such as depression, pain, and fatigue. There is compelling evidence that the gut microbiota affects cancer via several mechanisms, including microbial diversity and number, metabolism, and/or immune initiation. However, more research is necessary to elucidate these mechanisms, particularly among a variety of cancers and cancer-related symptoms. A better understanding of the role of the gut microbiota in cancer symptoms may lead to the development of targeted individualized interventions affecting the gut microbiota that prevent or ameliorate dysbiosis, thereby reducing symptoms. These interventions may emphasize self-care management strategies essential for wellness, such as diet, nutrition, and stress reduction.

Morita therapy for depression and anxiety (Morita Trial): study protocol for a pilot randomised controlled trial.

BackgroundMorita Therapy, a psychological therapy for common mental health problems, is in sharp contrast to established western psychotherapeutic approaches in teaching that undesired symptoms are natural features of human emotion rather than something to control or eliminate. The approach is widely practiced in Japan, but untested and little known in the UK. A clinical trial of Morita Therapy is required to establish the effectiveness of Morita Therapy for a UK population. However, a number of methodological, procedural and clinical uncertainties associated with such a trial first require addressing.Methods/DesignThe Morita Trial is a mixed methods study addressing the uncertainties associated with an evaluation of Morita Therapy compared with treatment as usual for depression and anxiety. We will undertake a pilot randomised controlled trial with embedded qualitative study. Sixty participants with major depressive disorder, with or without anxiety disorders, will be recruited predominantly from General Practice record searches and randomised to receive Morita Therapy plus treatment as usual or treatment as usual alone. Morita Therapy will be delivered by accredited psychological therapists. We will collect quantitative data on depressive symptoms, general anxiety, attitudes and quality of life at baseline and four month follow-up to inform future sample size calculations; and rates of recruitment, retention and treatment adherence to assess feasibility. We will undertake qualitative interviews in parallel with the trial, to explore people’s views of Morita Therapy. We will conduct separate and integrated analyses on the quantitative and qualitative data.DiscussionThe outcomes of this study will prepare the ground for the design and conduct of a fully-powered evaluation of Morita Therapy plus treatment as usual versus treatment as usual alone, or inform a conclusion that such a trial is not feasible and/or appropriate. We will obtain a more comprehensive understanding of these issues than would be possible from either a quantitative or qualitative approach alone.Trial registrationCurrent Controlled Trials ISRCTN17544090 registered on 23 July 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1279-3) contains supplementary material, which is available to authorized users.

Enhancing endothelialization by promoting endothelial cell competitiveness and endothelial function on soft polyelectrolyte multilayer film with matrix-bound VEGF

Event Abstract Back to Event Enhancing endothelialization by promoting endothelial cell competitiveness and endothelial function on soft polyelectrolyte multilayer film with matrix-bound VEGF Hao Chang1*, Kefeng Ren1*, Mi Hu1*, He Zhang1* and Jian Ji1* 1 Zhejiang University, Department of Polymer Science & Engineering, China Rapid endothelialization of vascular implant has been regarded as an efficient solution to eliminate undesired post-implanting symptoms[1]. Promoting endothelial cell (EC) competitiveness over smooth muscle cell (SMC)[2],[3] and subsequent endothelial function[4] play significant role in success of rapid-endothelialization. To this end, we employed poly(L-lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film (PEM)[5] with low crosslinking degrees as soft substrate and incorporated vascular endothelial growth factor (VEGF) in soft PEM in a matrix-bound manner. Adhesion and spread of both ECs and SMCs were promoted on the PEM with matrix-bound VEGF, which was associated with VEGF receptor 2. By regulating amount of VEGF incorporated in the PEM, selective EC adhesion was achieved. In addition, ECs were proliferating on PEM with matrix-bound VEGF while SMCs did not, which indicated that PEM with matrix-bound VEGF could efficiently promote EC competitiveness over SMC. Furthermore, the formed EC monolayer on the PEM with matrix-bound VEGF showed better integrity, higher release level of nitric oxide and higher expression level of endothelial function related genes than those on the substrates with high stiffness, which highlighted the benefit of soft substrate in endothelial function. This study provided a promising strategy of surface modification for enhancing endothelialization by promoting both EC competitiveness and endothelial function, which is of great potential in developing a new generation of vascular implants. Zhejiang Provincial Natural Science Foundation of China (LR15E030002); National Natural Science Foundation of China (51333005, 21374095); the National Basic Research Program of China (2011CB606203); International Science & Technology Cooperation Program of China (2014DFG52320)

17beta-estradiol loaded poly(lactic-co-glycolic acid) nanoparticles for cognitive therapy

17beta-estradiol loaded poly(lactic-co-glycolic acid) nanoparticles for cognitive therapy

ENDODONTIC PASTE PENETRATION BOTH IN MAXILLARY SINUS AND MANDIBULAR CANAL: REPORT OF A CASE TREATED BY PIEZOSURGERY

Endodontic incorrect preparation and overfilling can cause root canal filling material pushing into the adjacent vital anatomical structures such as maxillary sinus and mandibular canal. This condition can cause undesirable sensitivity symptoms. Although in some cases spontaneous resorption of some materials has been described; surgically removing the material presents the most favorable prognosis. In this study; a case of endodontic paste penetration both in maxillary sinus and mandibular canal which was treated by piezosurgery is presented

Adipose-Derived Stem Cells Decrease Bone Morphogenetic Protein Type 2-Induced Inflammation In Vivo

Recombinant human bone morphogenetic protein type 2 (rhBMP-2) has been used to promote bone regeneration. In contrast, some reports have suggested rhBMP-2 does not provide advantages over autogenous bone grafting owing to the undesirable postoperative symptoms of this growth factor. Because the undesirable symptoms of rhBMP-2 are usually promoted by inflammation, this study evaluated the in vivo effect of human adipose-derived stem cells (ASCs) incorporated into polylactic co-glycolic acid (PLGA) scaffolds in decreasing the inflammatory response induced by a low dose of rhBMP-2. PLGA scaffolds were characterized and loaded with rhBMP-2 1, 2.5, or 5 μg per scaffold (n = 6) and the in vitro released protein amounts were quantified at 7 hours and 1, 7, and 21 days after loading (n = 3). The muscle tissue of 6 beagles received the following treatments: PLGA, PLGA plus rhBMP-2 (2.5 μg), and PLGA plus rhBMP-2 plus ASCs (1 × 10(6) ASCs). The samples were evaluated 45 days after surgery. Statistical analyses were performed and the P value was set at .05. PLGA plus rhBMP-2 plus ASCs yielded the smallest number of inflammatory foci (P < .001) and giant cells (P < .001) and the largest number of angiogenesis sites (P < .001). Human ASCs administered in vivo into PLGA scaffolds with a low dose of rhBMP-2 decrease tissue inflammation and increase angiogenesis in muscular sites.

Defining the best candidates for testosterone replacement?

It is widely known that re-establishing physiologic levels of testosterone in symptomatic men with testosterone deficiency (TD) improves the undesirable symptoms associated with low testosterone. The indications for testosterone replacement therapy (TRT) have been evolving as research continues to find out who are the best candidates for therapy. Recently, concerns on the association of TRT and cardiovascular disease have received considerable attention. Before this, considerable attention had focused on the potential dangers of TRT and the risk of prostate cancer. The vast majority of contemporary evidence suggests that men with treated prostate cancer and no evidence of active disease are appropriate candidates for TRT in the context of symptomatic TD. Further, current evidence does not support denying TRT to symptomatic men with TD based on stable cardiac disease.

Comparison of two different folic acid doses with methotrexate--a randomized controlled trial (FOLVARI Study).

IntroductionThere is reasonable evidence that folic acid 5–10 mg per week leads to reduction in methotrexate (MTX) toxicity in rheumatoid arthritis (RA). However, this is based on studies conducted with lower MTX dosage than used currently. It is unclear whether higher doses of folic acid may be better in reducing toxicity.MethodsThis was a double-blind randomized controlled trial of 24 weeks duration. To be eligible, patients should have rheumatoid arthritis (1987 American College of Rheumatology criteria), be 18–75 years of age, not be on MTX and have active disease as defined by ‘Modified Disease Activity Score using three variables’ (DAS28(3)) > 3.2. MTX was started at 10 mg/week and escalated to 25 mg/week by 12 weeks. Folic acid was given at a dose of 10 mg (FA10) or 30 mg per week (FA30). Co-primary endpoints were incidence of toxicity (undesirable symptoms and laboratory abnormalities) and change in disease activity by 24 weeks. Intention-to-treat and per-protocol analyses were performed.ResultsAmong 100 patients enrolled, 51 and 49 were randomized to FA10 and FA30 respectively. By 24 weeks, there were 6 patient withdrawals in either group and mean(±SD) dose of MTX was 22.8 ± 4.4 and 21.4 ± 4.6 mg per week (p = 0.1). Frequency of patients with undesirable symptoms was non-significantly lower by 7.4 % (95 % confidence interval −27.4 to 12.7 %) in FA10 compared to FA30. There was also no difference in frequency of transaminitis (>Upper limit of normal (ULN)) (42.6, 45.7 %, p = 0.7) or transminitis as per primary endpoint (>2xULN) (10.6, 8.7 %, p = 1.0) or cytopenias (4.3, 4.3 %, p = 0.9). There was no difference in the primary end-point of occurrence of any adverse effect (symptom or laboratory) in FA10 and FA30 (46.8, 54.3 %, p = 0.5). At 24 weeks, DAS28(3) declined in both groups by a similar extent (−1.1 ± 1.0, −1.3 ± 1.0, p = 0.2) and ‘European League Against Rheumatism’ good or moderate response occurred in 56.9 and 67.4 % (p = 0.3).ConclusionsEven with the high doses of MTX used in current practice, there was no additional benefit (or harm) of a higher dose of folic acid (30 mg/week) over a usual dose (10 mg/week).Trial RegistrationClinicaltrials.gov NCT01583959 Registered 15 March 2012

A large-scale survey of adverse events experienced in yoga classes.

BackgroundYoga is a representative mind-body therapy of complementary and alternative medicine. In Japan, yoga is practiced widely to promote health, but yoga-associated adverse events have also been reported. To date, the frequencies and characteristics of yoga-related adverse events have not been elucidated. This study was conducted to elucidate the frequencies and characteristics of adverse events of yoga performed in classes and the risk factors of such events.MethodsThe subjects were 2508 people taking yoga classes and 271 yoga therapists conducting the classes. A survey for yoga class attendees was performed on adverse events that occurred during a yoga class on the survey day. A survey for yoga therapists was performed on adverse events that the therapists had observed in their students to date. Adverse events were defined as “undesirable symptoms or responses that occurred during a yoga class”.ResultsAmong 2508 yoga class attendees, 1343 (53.5%) had chronic diseases and 1063 (42.3%) were receiving medication at hospitals. There were 687 class attendees (27.8%) who reported some type of undesirable symptoms after taking a yoga class. Musculoskeletal symptoms such as myalgia were the most common symptoms, involving 297 cases, followed by neurological symptoms and respiratory symptoms. Most adverse events (63.8%) were mild and did not interfere with class participation. The risk factors for adverse events were examined, and the odds ratios for adverse events were significantly higher in attendees with chronic disease, poor physical condition on the survey day, or a feeling that the class was physically and mentally stressful. In particular, the occurrence of severe adverse events that interfered with subsequent yoga practice was high among elderly participants (70 years or older) and those with chronic musculoskeletal diseases.ConclusionsThe results of this large-scale survey demonstrated that approximately 30% of yoga class attendees had experienced some type of adverse event. Although the majority had mild symptoms, the survey results indicated that attendees with chronic diseases were more likely to experience adverse events associated with their disease. Therefore, special attention is necessary when yoga is introduced to patients with stress-related, chronic diseases.

Can oral corticosteroids reduce the severity or duration of an acute cough, and the associated National Health Service and societal costs, in adults presenting to primary care? Study protocol for a randomised controlled trial.

BackgroundAcute lower respiratory tract infection (LRTI) is one of the most common conditions managed internationally and is costly to health services and patients. Despite good evidence that antibiotics are not effective for improving the symptoms of uncomplicated LRTI, they are widely prescribed, contributing to antimicrobial resistance. Many of the symptoms observed in LRTI are mediated by inflammatory processes also observed in exacerbations of asthma, for which there is strong evidence of corticosteroid effectiveness. The primary aim of the OSAC (Oral Steroids for Acute Cough) Trial is to determine whether oral prednisolone (40 mg daily for 5 days) can reduce the duration of moderately bad (or worse) cough and the severity of all its associated symptoms on days 2 to 4 post-randomisation (day 1 is trial entry) by at least 20% in adults ≥18 years with acute LRTI presenting to primary care.Methods/designOSAC is a two-arm, multi-centre, placebo-controlled, randomised superiority trial. The target sample size is 436 patients, which allows for a 20% dropout rate. Patients will be recruited from primary care sites (General Practitioner surgeries) across England and followed up until symptom resolution. The two primary clinical outcomes are the duration of moderately bad (or worse) cough, and the severity of all its associated symptoms on days 2 to 4 post-randomisation. Secondary outcomes include: antibiotic consumption; symptom burden; adverse events; participant satisfaction with treatment and intention to consult for future similar illnesses. A parallel economic evaluation will investigate the cost-effectiveness of the intervention.DiscussionResults from the OSAC trial will increase knowledge regarding the clinical and cost-effectiveness of corticosteroids for LRTI, and will establish the potential of a new treatment option that could substantially improve patient health. We have chosen a relatively high ‘efficacy dose’ as this will enable us to decide on the potential for further research into lower dose oral and/or inhaled corticosteroids. This trial will also contribute to a growing body of research investigating the natural course of this very common illness, as well as the effects of steroids on the undesirable inflammatory symptoms associated with infection.Trial registrationCurrent Controlled Trials ISRCTN57309858 (31 January 2013).Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-015-0569-5) contains supplementary material, which is available to authorized users.

Patients' oral hydration levels and incidence of immediate to short-term mild side-effects in contrast agent enhanced MRI diagnostics

AimGadolinium-based contrast agents for radiodiagnostic purposes can lead to side effects, including nephrotoxicity in patients with renal insufficiency. This study evaluated whether the occurrence of mild side effects from gadolinium-based contrast enhanced magnetic resonance imaging (MRI) correlates to patients' oral hydration levels. MethodsOral fluid intake levels 24 h pre- and 24 h post-MRI, as well as incidence of mild side-effects experienced 30 min and 24 h post-MRI were recorded by using a patient self-reporting questionnaire. ResultsA total of 174 patients, 29 controls, 98 administered Prohance and 47 receiving Dotarem, were enrolled. Overall, the most frequently reported side-effect was headache; nausea only occurred in patients receiving contrast agent. One or more side-effects experienced 24 h following the MRI scan were reported by 10% (controls), 24% (Prohance) and 22% (Dotarem) of patients, respectively. Multivariate ordinal regression analysis showed that only male gender (OR 0.24, 95% CI 0.11–0.53) was statistically significantly associated with a decreased incidence of side-effects 30 min after MRI. At 24-h post MRI, a lack of contrast agent (OR 0.40, 95% CI 0.09–1.74) and male gender (OR 0.46, 95% CI 0.19–1.09) were associated with fewer side-effects. ConclusionsThe level oral fluid intake before and after undergoing gadolinium-based contrast-enhanced MRI does not appear to markedly affect the incidence of common undesirable mild symptoms experienced shortly after the procedure. Confounding differences between patients in reporting side-effects may contribute to these findings.