Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?

Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity. Yet, with regard to pharmacotherapy for obesity, we are far from true personalised medicine. We review the limited mechanistic data with four mono and combination pharmacotherapies, to assess the potential for tailoring their use to target specific obesogenic behaviours. Potential treatment options are considered, but in the absence of adequate research in respect to effects of these drugs on eating behaviour, neural activity and psychological substrates that underlie poorly controlled eating, we are far from definitive therapeutic recommendations. Specific mechanistic studies and broader behavioural phenotyping, possibly in conjunction with pharmacogenetic research, are required to characterise responders for distinct pharmacotherapeutic options

Postulated Vasoactive Neuropeptide Autoimmunity in Fatigue-Related Conditions: A Brief Review and Hypothesis

Disorders such as chronic fatigue syndrome (CFS) and gulf war syndrome (GWS) are characterised by prolonged fatigue and a range of debilitating symptoms of pain, intellectual and emotional impairment, chemical sensitivities and immunological dysfunction. Sudden infant death syndrome (SIDS) surprisingly may have certain features in common with these conditions. Post-infection sequelae may be possible contributing factors although ongoing infection is unproven. Immunological aberration may prove to be associated with certain vasoactive neuropeptides (VN) in the context of molecular mimicry, inappropriate immunological memory and autoimmunity

Specific treatment of problems of the spine (STOPS): design of a randomised controlled trial comparing specific physiotherapy versus advice for people with subacute low back disorders

<p>Abstract</p> <p>Background</p> <p>Low back disorders are a common and costly cause of pain and activity limitation in adults. Few treatment options have demonstrated clinically meaningful benefits apart from advice which is recommended in all international guidelines. Clinical heterogeneity of participants in clinical trials is hypothesised as reducing the likelihood of demonstrating treatment effects, and sampling of more homogenous subgroups is recommended. We propose five subgroups that allow the delivery of specific physiotherapy treatment targeting the pathoanatomical, neurophysiological and psychosocial components of low back disorders. The aim of this article is to describe the methodology of a randomised controlled trial comparing specific physiotherapy treatment to advice for people classified into five subacute low back disorder subgroups.</p> <p>Methods/Design</p> <p>A multi-centre parallel group randomised controlled trial is proposed. A minimum of 250 participants with subacute (6 weeks to 6 months) low back pain and/or referred leg pain will be classified into one of five subgroups and then randomly allocated to receive either physiotherapy advice (2 sessions over 10 weeks) or specific physiotherapy treatment (10 sessions over 10 weeks) tailored according to the subgroup of the participant. Outcomes will be assessed at 5 weeks, 10 weeks, 6 months and 12 months following randomisation. Primary outcomes will be activity limitation measured with a modified Oswestry Disability Index as well as leg and back pain intensity measured on separate 0-10 Numerical Rating Scales. Secondary outcomes will include a 7-point global rating of change scale, satisfaction with physiotherapy treatment, satisfaction with treatment results, the Sciatica Frequency and Bothersomeness Scale, quality of life (EuroQol-5D), interference with work, and psychosocial risk factors (Orebro Musculoskeletal Pain Questionnaire). Adverse events and co-interventions will also be measured. Data will be analysed according to intention to treat principles, using linear mixed models for continuous outcomes, Mann Whitney U tests for ordinal outcomes, and Chi-square, risk ratios and risk differences for dichotomous outcomes.</p> <p>Discussion</p> <p>This trial will determine the difference in outcomes between specific physiotherapy treatment tailored to each of the five subgroups versus advice which is recommended in guidelines as a suitable treatment for most people with a low back disorder.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000834257.aspx">ACTRN12609000834257</a>.</p

Prevalence of vertebral deformities and symptomatic vertebral fractures in corticosteroid treated patients with rheumatoid arthritis

Objective. This study was designed to determine whether the prevalence of vertebral deformities in patients with rheumatoid arthritis (RA) treated with corticosteroids (Cs) is higher than in RA patients not receiving Cs therapy. Patients and methods. This multicentre cross-sectional study included 205 patients with RA who were receiving Cs orally on a daily basis and 205 patients with RA who did not receive Cs, matched for sex and age. Vertebral deformities were scored according to the Kleerekoper method. Results. Vertebral deformities were found in 52 (25%) patients on Cs and in 26 (13%) patients not on Cs. Sixteen (8%) patients in the group on Cs had experienced clinical manifestations of an acute vertebral fracture in the past vs only three patients (1.5%) among those not on Cs. The use of Cs tended to increase the risk of developing a vertebral deformity [adjusted odds ratio (OR) 1.56, 95% confidence interval (CI) 0.81-2.99] and symptomatic vertebral fracture (adjusted OR 1.42, 95% CI 0.24-8.32). Each 1-mg increase in the current daily Cs dose increased the risk of a vertebral deformity (adjusted OR 1.05, 95% CI 0.98-1.13) and of a symptomatic vertebral fracture (adjusted OR 1.05, 95% CI 0.89-1.24). Conclusion. There is a higher prevalence of vertebral deformities and clinical manifestations of vertebral fractures in patients on Cs than in those not on Cs. Our data indicate that the use of Cs and each 1-mg increase in the current daily Cs dose may increase the risk of development of a vertebral deformity and symptomatic vertebral fracture in patients with RA

Acceptability of a Rinse Screening Test for Diagnosing Head and Neck Squamous Cell Carcinoma Among Black Americans

Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease. We evaluated an easy-to-administer and innovative rinse that assays soluble CD44 and total protein as HNSCC early detection markers. We examined whether the rinse was acceptable and whether the results would promote screening behavior. This is a prospective observational study. Participants (N = 150) from underserved, low-income Black American backgrounds completed assessments of satisfaction, intention to repeat test, and likely screening behavior after receiving results. Descriptive statistics, t tests, and analysis of variance (ANOVA) were conducted. The rinse was highly acceptable to participants and perceived to be acceptable among peers. Participants strongly agreed that they would perform the rinse as prescribed, engage in preventative behaviors if results indicated risk of cancer, and initiate treatment if they had a positive cancer finding. Employed participants slightly disliked the taste of the rinse but were more likely to schedule a follow-up appointment and engage in preventative behaviors based on the results. Those with health-care coverage (including public health insurance) reported that the test was harder to perform than those who were uninsured. An easy-to-use rinse technique is acceptable and likely to promote screening behavior among Black Americans at risk for HNSCC. Given that many cancer screening modalities are considered unpleasant to undergo, this rinse holds promise for promoting screening behaviors and, thereby, may result in early detection of this potentially fatal disease. IV

The RNA Atlas expands the catalog of human non-coding RNAs

Existing compendia of non-coding RNA (ncRNA) are incomplete, in part because they are derived almost exclusively from small and polyadenylated RNAs. Here we present a more comprehensive atlas of the human transcriptome, which includes small and polyA RNA as well as total RNA from 300 human tissues and cell lines. We report thousands of previously uncharacterized RNAs, increasing the number of documented ncRNAs by approximately 8%. To infer functional regulation by known and newly characterized ncRNAs, we exploited pre-mRNA abundance estimates from total RNA sequencing, revealing 316 microRNAs and 3,310 long non-coding RNAs with multiple lines of evidence for roles in regulating protein-coding genes and pathways. Our study both refines and expands the current catalog of human ncRNAs and their regulatory interactions. All data, analyses and results are available for download and interrogation in the R2 web portal, serving as a basis for future exploration of RNA biology and function

Towards an integrated clinical framework for patient with shoulder pain

Abstract Background Shoulder pain (SP) represents a common musculoskeletal condition that requires physical therapy care. Along the years, the usual evaluation strategies based on clinical tests and diagnostic imaging has been challenged. Clinical tests appear unable to clearly identify the structures that generated pain and interpretation of diagnostic imaging is still controversial. The current patho-anatomical diagnostic categories have demonstrated poor reliability and seem inadequate for the SP treatment. Objectives The present paper aims to (1) describe the different proposals of clinical approach to SP currently available in the literature; to (2) integrate these proposals in a single framework in order to help the management of SP. Conclusion The proposed clinical framework, based on a bio-psychosocial vision of health, integrates symptoms characteristics, pain mechanisms and expectations, preferences and psychosocial factors of patients that may guide physiotherapist to make a diagnostic triage and to choose the right treatment for the individual patient