Efficacy and Safety of Tapencarium (RZL-012) in Submental Fat Reduction.

BACKGROUND: Tapencarium (RZL-012) (5-(3.6-dibromo-9H-carbazol-9-yl)-N, N, N-trimethylpentan-1-aminium chloride) is a novel injectable synthetic molecule with cytolytic properties, capable of reducing subcutaneous fat volume. OBJECTIVES: The goal of this 3-armed, randomized, double-blind, placebo-controlled phase 2b study was to determine the safety and efficacy of low- and high-dose RZL-012 vs placebo on submental fat (SMF) reduction. METHODS: Patients (n = 151, age 18-65 years) with excess SMF received a single treatment session of RZL-012 or placebo in the submental area, after which they were monitored for 84 days. SMF was assessed at baseline and after dosing with newly developed scales, namely the Clinician Chin Assessment Tool (C-CAT) and Subject Chin Assessment Tool (S-CAT). SMF was also assessed by magnetic resonance imaging (MRI) at screening and on Day 84 after treatment. RESULTS: The proportion of patients who had a 1-grade or 2-grade improvement in C-CAT and/or S-CAT on Day 84 vs baseline was significantly higher in the high-dose RZL-012 group vs the placebo group (P < .002). The relative percentage reduction in MRI-measured SMF volume (Day 84 vs screening) was significantly greater in the high-dose RZL-012 group vs the low-dose RZL-012 or the placebo group (P < .0001). Local injection site reactions were the most common adverse events (AEs). CONCLUSIONS: A single administration of RZL-012 into SMF resulted in significant improvement in submental appearance as assessed by clinicians, patients, and MRI. From a safety perspective, there were no serious AEs and no clinically significant changes in vital signs or laboratory tests over the course of the study.

Using a theoretical framework to develop postgraduate health professions education research and practice.

This article was migrated. The article was marked as recommended. Healthcare education is complex and multifaceted, requiring study from different angles and with different lenses. We propose that the use of a meta-framework can help those teaching and researching postgraduate health professions education make holistic sense of their practice and findings from different projects. We discuss how we have employed Bronfenbrenner's ecological systems theory (EST) as an overarching theoretical framework for the scholarship of learning and teaching in the context of postgraduate health professions education. Taking a structured approach to pedagogical thinking and research through the use of a meta-framework opens up useful ways of framing findings and further questions, locating research projects within a bigger picture, and communicating to others the focus of a research programme. We address the problem of the under-theorizing of educational research in postgraduate health professions education, advocating both theoretical frameworks for individual research projects, and an overarching theoretical "meta-framework" to interrogate and draw together multiple studies. In doing so we build on, critique and further develop Bronfenbrenner's ecological systems theory.

Mass spectrometry imaging of triglycerides in biological tissues by laser desorption ionization from silicon nanopost arrays.

Mass spectrometry imaging (MSI) is used increasingly to simultaneously detect a broad range of biomolecules while mapping their spatial distributions within biological tissue sections. Matrix-assisted laser desorption ionization (MALDI) is recognized as the method-of-choice for MSI applications due in part to its broad molecular coverage. In spite of the remarkable advantages offered by MALDI, imaging of neutral lipids, such as triglycerides (TGs), from tissue has remained a significant challenge due to ion suppression of TGs by phospholipids, e.g. phosphatidylcholines (PCs). To help overcome this limitation, silicon nanopost array (NAPA) substrates were introduced to selectively ionize TGs from biological tissue sections. This matrix-free laser desorption ionization (LDI) platform was previously shown to provide enhanced ionization of certain lipid classes, such as hexosylceramides (HexCers) and phosphatidylethanolamines (PEs) from mouse brain tissue. In this work, we present NAPA as an MSI platform offering enhanced ionization efficiency for TGs from biological tissues relative to MALDI, allowing it to serve as a complement to MALDI-MSI. Analysis of a standard lipid mixture containing PC(18:1/18:1) and TG(16:0/16:0/16:0) by LDI from NAPA provided an ~49 and ~227-fold higher signal for TG(16:0/16:0/16:0) relative to MALDI, when analyzed without and with the addition of a sodium acetate, respectively. In contrast, MALDI provided an ~757 and ~295-fold higher signal for PC(18:1/18:1) compared with NAPA, without and with additional Na+ . Averaged signal intensities for TGs from MSI of mouse lung and human skin tissues exhibited an ~105 and ~49-fold increase, respectively, with LDI from NAPA compared with MALDI. With respect to PCs, MALDI provided an ~2 and ~19-fold increase in signal intensity for mouse lung and human skin tissues, respectively, when compared with NAPA. The complementary coverage obtained by the two platforms demonstrates the utility of using both techniques to maximize the information obtained from lipid MS or MSI experiments.

Effects of mindfulness training programmes delivered by a self-directed mobile app and by telephone compared with an education programme for survivors of critical illness: a pilot randomised clinical trial.

BACKGROUND: Patients who are sick enough to be admitted to an intensive care unit (ICU) commonly experience symptoms of psychological distress after discharge, yet few effective therapies have been applied to meet their needs. METHODS: Pilot randomised clinical trial with 3-month follow-up conducted at two academic medical centres. Adult (≥18 years) ICU patients treated for cardiorespiratory failure were randomised after discharge home to 1 of 3 month-long interventions: a self-directed mobile app-based mindfulness programme; a therapist-led telephone-based mindfulness programme; or a web-based critical illness education programme. RESULTS: Among 80 patients allocated to mobile mindfulness (n=31), telephone mindfulness (n=31) or education (n=18), 66 (83%) completed the study. For the primary outcomes, target benchmarks were exceeded by observed rates for all participants for feasibility (consent 74%, randomisation 91%, retention 83%), acceptability (mean Client Satisfaction Questionnaire 27.6 (SD 3.8)) and usability (mean Systems Usability Score 89.1 (SD 11.5)). For secondary outcomes, mean values (and 95% CIs) reflected clinically significant group-based changes on the Patient Health Questionnaire depression scale (mobile (-4.8 (-6.6, -2.9)), telephone (-3.9 (-5.6, -2.2)), education (-3.0 (-5.3, 0.8)); the Generalized Anxiety Disorder scale (mobile -2.1 (-3.7, -0.5), telephone -1.6 (-3.0, -0.1), education -0.6 (-2.5, 1.3)); the Post-Traumatic Stress Scale (mobile -2.6 (-6.3, 1.2), telephone -2.2 (-5.6, 1.2), education -3.5 (-8.0, 1.0)); and the Patient Health Questionnaire physical symptom scale (mobile -5.3 (-7.0, -3.7), telephone -3.7 (-5.2, 2.2), education -4.8 (-6.8, 2.7)). CONCLUSIONS: Among ICU patients, a mobile mindfulness app initiated after hospital discharge demonstrated evidence of feasibility, acceptability and usability and had a similar impact on psychological distress and physical symptoms as a therapist-led programme. A larger trial is warranted to formally test the efficacy of this approach. TRIAL REGISTRATION NUMBER: Results, NCT02701361.

Can the Electron-Accepting Properties of Odorants Be Involved in Their Recognition by the Olfactory System?

The present study examines the possible importance of the electron-accepting properties of odorant molecules and, in particular, the formation and decay of temporary negative ions via low-energy electron attachment as a possible contribution toward understanding odorant recognition by olfactory receptors (ORs). Fragments formed by dissociative electron attachment (DEA) of mustard oil odorants represented by a series of isothiocyanates are studied experimentally using DEA spectroscopy and DFT calculations. Relative intensities for the most abundant fragment species, S- and SCN-, are found to be characteristic of structurally similar odorants under investigation. This novel approach for the investigation of odorants may contribute to understanding the initial stages of the olfactory process and may provide a means to distinguish between odorants and their interactions with the olfactory receptor system.

Prevention and Management of Injection-Related Adverse Effects in Facial Aesthetics: Considerations for ATX-101 (Deoxycholic Acid Injection) Treatment.

ATX-101 (deoxycholic acid injection; Kythera Biopharmaceuticals, Inc. [an affiliate of Allergan plc, Dublin, Ireland]) was approved in 2015 in the United States (Kybella) and Canada (Belkyra) for submental fat reduction. As expected, injection-site reactions such as pain, swelling, and bruising, which were mostly mild or moderate and transient, were common adverse events (AEs) reported in clinical trials. An exploratory Phase 3b study investigating interventions for management of injection-site AEs associated with ATX-101 treatment was recently completed. Based on its results, literature review, and our clinical experiences, we have put forward considerations for management of AEs associated with ATX-101 treatment in clinical practice. Pretreatment with oral ibuprofen and/or acetaminophen an hour before treatment and preinjection with epinephrine-containing buffered lidocaine 15 minutes before treatment can help with management of pain and bruising. Cold application to the treated area before and immediately after the procedure may help to reduce pain (if local anesthetic preinjection is not performed) and swelling. Discontinuing medications/supplements that result in increased anticoagulant or antiplatelet activity 7 to 10 days before ATX-101 treatment, when possible, can reduce the risk of bruising. In summary, injection-site AEs associated with ATX-101 treatment can be effectively managed with commonly used interventions.

Development and preliminary evaluation of a telephone-based mindfulness training intervention for survivors of critical illness.

RATIONALE: Persistent symptoms of psychological distress represent an unmet need among intensive care unit (ICU) survivors. OBJECTIVES: We aimed to develop and pilot test a simple telephone-based mindfulness training intervention to address this population's unique needs. METHODS: Open trial involving survivors of medical and surgical critical illness and their informal caregivers, using a pretest-posttest design. MEASUREMENTS AND MAIN RESULTS: We developed a six-session, telephone-delivered, ICU survivor-specific mindfulness intervention based on past focus groups, the medical literature, and the precedent of the most effective components of existing mindfulness programs. A total of 11 survivors of mechanical ventilation were enrolled, together with 2 informal caregivers for exploratory purposes. Three patients dropped out before intervention initiation because of progressive illness or severe social stressors. Of the 10 remaining participants, 8 (80%) completed the program within 7 weeks. Among these eight patients and caregivers who completed all study procedures, six (75%) experienced improvement in symptoms of psychological distress (anxiety, depression, or post-traumatic stress disorder). Changes in distress symptoms were correlated with improvement in mindfulness qualities, adaptive coping, and emotion regulation. Participants reported high satisfaction with the program in postintervention interviews. CONCLUSIONS: A new ICU survivor-specific mindfulness training intervention delivered by telephone was acceptable and feasible. Changes in symptoms of distress were correlated with changes in skills that were targeted by the mindfulness program. Controlled trials are needed to further evaluate this promising intervention.

Guidance on the management of pain in older people.

This guidance document reviews the epidemiology and management of pain in older people via a literature review of published research. The aim of this document is to inform health professionals in any care setting who work with older adults on best practice for the management of pain and to identify where there are gaps in the evidence that require further research. The assessment of pain in older people has not been covered within this guidance and can be found in a separate document (http://www.britishpainsociety.org/pub_professional.htm#assessmentpop). Substantial differences in the population, methods and definitions used in published research makes it difficult to compare across studies and impossible to determine the definitive prevalence of pain in older people. There are inconsistencies within the literature as to whether or not pain increases or decreases in this age group, and whether this is influenced by gender. There is, however, some evidence that the prevalence of pain is higher within residential care settings. The three most common sites of pain in older people are the back; leg/knee or hip and 'other' joints. In common with the working-age population, the attitudes and beliefs of older people influence all aspects of their pain experience. Stoicism is particularly evident within this cohort of people. Evidence from the literature search suggests that paracetamol should be considered as first-line treatment for the management of both acute and persistent pain, particularly that which is of musculoskeletal origin, due to its demonstrated efficacy and good safety profile. There are few absolute contraindications and relative cautions to prescribing paracetamol. It is, however, important that the maximum daily dose (4 g/24 h) is not exceeded. Non-selective non-steroidal anti-inflammatory drugs (NSAIDs) should be used with caution in older people after other safer treatments have not provided sufficient pain relief. The lowest dose should be provided, for the shortest duration. For older adults, an NSAID or cyclooxygenase-2 (COX-2) selective inhibitor should be co-prescribed with a proton pump inhibitor (PPI), and the one with the lowest acquisition cost should be chosen. All older people taking NSAIDs should be routinely monitored for gastrointestinal, renal and cardiovascular side effects, and drug­drug and drug­disease interactions. Opioid therapy may be considered for patients with moderate or severe pain, particularly if the pain is causing functional impairment or is reducing their quality of life. However, this must be individualised and carefully monitored. Opioid side effects including nausea and vomiting should be anticipated and suitable prophylaxis considered. Appropriate laxative therapy, such as the combination of a stool softener and a stimulant laxative, should be prescribed throughout treatment for all older people who are prescribed opioid therapy. Tricyclic antidepressants and anti-epileptic drugs have demonstrated efficacy in several types of neuropathic pain. But, tolerability and adverse effects limit their use in an older population. Intra-articular corticosteroid injections in osteoarthritis of the knee are effective in relieving pain in the short term, with little risk of complications and/or joint damage. Intra-articular hyaluronic acid is effective and free of systemic adverse effects. It should be considered in patients who are intolerant to systemic therapy. Intra-articular hyaluronic acid appears to have a slower onset of action than intra-articular steroids, but the effects seem to last longer. The current evidence for the use of epidural steroid injections in the management of sciatica is conflicting and, until further larger studies become available, no firm recommendations can be made. There is, however, a limited body of evidence to support the use of epidural injections in spinal stenosis. The literature review suggests that assistive devices are widely used and that the ownership of devices increases with age. Such devices enable older people with chronic pain to live in the community. However, they do not necessarily reduce pain and can increase pain if used incorrectly. Increasing activity by way of exercise should be considered. This should involve strengthening, flexibility, endurance and balance, along with a programme of education. Patient preference should be given serious consideration. A number of complementary therapies have been found to have some efficacy among the older population, including acupuncture, transcutaneous electrical nerve stimulation (TENS) and massage. Such approaches can affect pain and anxiety and are worth further investigation. Some psychological approaches have been found to be useful for the older population, including guided imagery, biofeedback training and relaxation. There is also some evidence supporting the use of cognitive behavioural therapy (CBT) among nursing home populations, but of course these approaches require training and time. There are many areas that require further research, including pharmacological management where approaches are often tested in younger populations and then translated across. Prevalence studies need consistency in terms of age, diagnosis and terminology, and further work needs to be done on evaluating non-pharmacological approaches.

Volumizing the face with soft tissue fillers.

This article discusses the role of injectable soft-tissue fillers in the aging face, and their clinical and chemical behavior. Temporary and permanent fillers are discussed, namely hyaluronic acids, calcium hydroxylapatite, poly-l-lactic acid, liquid silicone, and polymethylmethacrylate. Techniques and outcomes are presented.