Double-blind randomised controlled trial of percutaneous tibial nerve stimulation versus sham electrical stimulation in the treatment of faecal incontinence: CONtrol of Faecal Incontinence using Distal NeuromodulaTion (the CONFIDeNT trial)

Background: Faecal incontinence (FI) is a common condition which is often under-reported. It is distressing for those suffering from it, impacting heavily on their quality of life. When conservative strategies fail, treatment options are limited. Percutaneous tibial nerve stimulation (PTNS) is a minimally invasive outpatient treatment, shown in preliminary case series to have significant effectiveness; however, no randomised controlled trial has been conducted. Objectives: To assess the effectiveness of PTNS compared with sham electrical stimulation in the treatment of patients with FI in whom initial conservative strategies have failed. Design: Multicentre, parallel-arm, double-blind randomised (1 : 1) controlled trial. Setting: Eighteen UK centres providing specialist nurse-led (or equivalent) treatment for pelvic floor disorders. Participants: Participants aged > 18 years with FI who have failed conservative treatments and whose symptoms are sufficiently severe to merit further intervention. Interventions: PTNS was delivered via the Urgent® PC device (Uroplasty Limited, Manchester, UK), a hand-held pulse generator unit, with single-use leads and fine-needle electrodes. The needle was inserted near the tibial nerve on the right leg adhering to the manufacturer’s protocol (and specialist training). Treatment was for 30 minutes weekly for a duration of 12 treatments. Validated sham stimulation involved insertion of the Urgent PC needle subcutaneously at the same site with electrical stimulation delivered to the distal foot using transcutaneous electrical nerve stimulation. Main outcome measures: Outcome measures were assessed at baseline and 2 weeks following treatment. Clinical outcomes were derived from bowel diaries and validated, investigator-administered questionnaires. The primary outcome classified patients as responders or non-responders, with a responder defined as someone having achieved ≥ 50% reduction in weekly faecal incontinence episodes (FIEs). Results: In total, 227 patients were randomised from 373 screened: 115 received PTNS and 112 received sham stimulation. There were 12 trial withdrawals: seven from the PTNS arm and five from the sham arm. Missing data were multiply imputed. For the primary outcome, the proportion of patients achieving a ≥ 50% reduction in weekly FIEs was similar in both arms: 39 in the PTNS arm (38%) compared with 32 in the sham arm (31%) [odds ratio 1.28, 95% confidence interval (CI) 0.72 to 2.28; p = 0.396]. For the secondary outcomes, significantly greater decreases in weekly FIEs were observed in the PTNS arm than in the sham arm (beta –2.3, 95% CI –4.2 to –0.3; p = 0.02), comprising a reduction in urge FIEs (p = 0.02) rather than passive FIEs (p = 0.23). No significant differences were found in the St Mark’s Continence Score or any quality-of-life measures. No serious adverse events related to treatment were reported. Conclusions: PTNS did not show significant clinical benefit over sham electrical stimulation in the treatment of FI based on number of patients who received at least a 50% reduction in weekly FIE. It would be difficult to recommend this therapy for the patient population studied. Further research will concentrate on particular subgroups of patients, for example those with pure urge FI. Trial registration: Current Controlled Trials ISRCTN88559475. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 77. See the NIHR Journals Library website for further project information

Mafic magma feeds degassing unrest at Vulcano Island, Italy

The benign fuming activity of dormant volcanoes is punctuated by phases of escalating degassing activity that, on some occasions, ultimately prelude to eruption. However, understanding the drivers of such unrest is complicated by complex interplay between magmatic and hydrothermal processes. Some of the most comprehensively characterised degassing unrest have recently been observed at La Fossa cone on Vulcano Island, but whether or not these episodes involve new, volatile-rich ascending magma remains debated. Here, we use volcanic gas measurements, in combination with melt inclusion information, to propose that heightened sulphur dioxide flux during the intense fall 2021 La Fossa unrest is sourced by degassing of volatile-rich mafic magma. Calculations using a numerical model indicate observations are consistent with the unrest being triggered by the emplacement of ∼3·106 m3 of mafic magma at ∼4–5 km depth. Degassing of mafic magma is argued as a recurrent driver of unrest at dormant volcanoes worldwide

The Role of Medical Language in Changing Public Perceptions of Illness

This study was designed to investigate the impact of medical terminology on perceptions of disease. Specifically, we look at the changing public perceptions of newly medicalized disorders with accompanying newly medicalized terms (e.g. impotence has become erectile dysfunction disorder). Does using “medicalese” to label a recently medicalized disorder lead to a change in the perception of that condition? Undergraduate students (n = 52) rated either the medical or lay label for recently medicalized disorders (such as erectile dysfunction disorder vs. impotence) and established medical conditions (such as a myocardial infarction vs. heart attack) for their perceived seriousness, disease representativeness and prevalence. Students considered the medical label of the recently medicalized disease to be more serious (mean = 4.95 (SE = .27) vs. mean = 3.77 (SE = .24) on a ten point scale), more representative of a disease (mean = 2.47 (SE = .09) vs. mean = 1.83 (SE = .09) on a four point scale), and have lower prevalence (mean = 68 (SE = 12.6) vs. mean = 122 (SE = 18.1) out of 1,000) than the same disease described using common language. A similar pattern was not seen in the established medical conditions, even when controlled for severity. This study demonstrates that the use of medical language in communication can induce bias in perception; a simple switch in terminology results in a disease being perceived as more serious, more likely to be a disease, and more likely to be a rare condition. These findings regarding the conceptualization of disease have implications for many areas, including medical communication with the public, advertising, and public policy

Male synthetic sling versus artificial urinary sphincter trial for men with urodynamic stress incontinence after prostate surgery (MASTER): Study protocol for a randomised controlled trial

© 2018 The Author(s). Background: Stress urinary incontinence (SUI) is a frequent adverse effect for men undergoing prostate surgery. A large proportion (around 8% after radical prostatectomy and 2% after transurethral resection of prostate (TURP)) are left with severe disabling incontinence which adversely effects their quality of life and many are reliant on containment measures such as pads (27% and 6% respectively). Surgery is currently the only option for active management of the problem. The overwhelming majority of surgeries for persistent bothersome SUI involve artificial urinary sphincter (AUS) insertion. However, this is expensive, and necessitates manipulation of a pump to enable voiding. More recently, an alternative to AUS has been developed - a synthetic sling for men which elevates the urethra, thus treating SUI. This is thought, by some, to be less invasive, more acceptable and less expensive than AUS but clear evidence for this is lacking. The MASTER trial aims to determine whether the male synthetic sling is non-inferior to implantation of the AUS for men who have SUI after prostate surgery (for cancer or benign disease), judged primarily on clinical effectiveness but also considering relative harms and cost-effectiveness. Methods/design: Men with urodynamic stress incontinence (USI) after prostate surgery, for whom surgery is judged appropriate, are the target population. We aim to recruit men from secondary care urological centres in the UK NHS who carry out surgery for post-prostatectomy incontinence. Outcomes will be assessed by participant-completed questionnaires and 3-day urinary bladder diaries at baseline, 6, 12 and 24 months. The 24-h urinary pad test will be used at baseline as an objective assessment of urine loss. Clinical data will be completed at the time of surgery to provide details of the operative procedures, complications and resource use in hospital. At 12 months, men will also have a clinical review to evaluate the results of surgery (including another 24-h pad test) and to identify problems or need for further treatment. Discussion: A robust examination of the comparative effectiveness of the male synthetic sling will provide high-quality evidence to determine whether or not it should be adopted widely in the NHS

High-Throughput Sequencing, Characterization and Detection of New and Conserved Cucumber miRNAs

Micro RNAS (miRNAs) are a class of endogenous small non coding RNAs involved in the post-transcriptional regulation of gene expression. In plants, a great number of conserved and specific miRNAs, mainly arising from model species, have been identified to date. However less is known about the diversity of these regulatory RNAs in vegetal species with agricultural and/or horticultural importance

A systematic review of interventions to increase awareness of mental health and well-being in athletes, coaches and officials

Full search for the psychinfo database. (DOCX 16 kb

Pemphigus autoimmunity: Hypotheses and realities

The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients