Does offering an incentive payment improve recruitment to clinical trials and increase the proportion of socially deprived and elderly participants?

BACKGROUND: Patient recruitment into clinical trials is a major challenge, and the elderly, socially deprived and those with multiple comorbidities are often underrepresented. The idea of paying patients an incentive to participate in research is controversial, and evidence is needed to evaluate this as a recruitment strategy. METHOD: In this study, we sought to assess the impact on clinical trial recruitment of a £100 incentive payment and whether the offer of this payment attracted more elderly and socially deprived patients. A total of 1,015 potential patients for five clinical trials (SCOT, FAST and PATHWAY 1, 2 and 3) were randomised to receive either a standard trial invitation letter or a trial invitation letter containing an incentive offer of £100. To receive payment, patients had to attend a screening visit and consent to be screened (that is, sign a consent form). To maintain equality, eventually all patients who signed a consent form were paid £100. RESULTS: The £100 incentive offer increased positive response to the first invitation letter from 24.7% to 31.6%, an increase of 6.9% (P < 0.05). The incentive offer increased the number of patients signing a consent form by 5.1% (P < 0.05). The mean age of patients who responded positively to the invitation letter was 66.5 ± 8.7 years, whereas those who responded negatively were significantly older, with a mean age of 68.9 ± 9.0 years. The incentive offer did not influence the age of patients responding. The incentive offer did not improve response in the most socially deprived areas, and the response from patients in these areas was significantly lower overall. CONCLUSION: A £100 incentive payment offer led to small but significant improvements in both patient response to a clinical trial invitation letter and in the number of patients who consented to be screened. The incentive payment did not attract elderly or more socially deprived patients. TRIAL REGISTRATIONS: Standard care versus Celecoxib Outcome Trial (SCOT) (ClinicalTrials.gov identifier: NCT00447759). Febuxostat versus Allopurinol Streamlined Trial (FAST) (EudraCT number: 2011-001883-23). Prevention and Treatment of Hypertension with Algorithm Guided Therapy (British Heart Foundation funded trials) (PATHWAY) 1: Monotherapy versus dual therapy for initiating treatment (EudraCT number: 2008-007749-29). PATHWAY 2: Optimal treatment of drug-resistant hypertension (EudraCT number: 2008-007149-30). PATHWAY 3: Comparison of single and combination diuretics in low-renin hypertension (EudraCT number: 2009-010068-41). ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13063-015-0582-8) contains supplementary material, which is available to authorized users

From presence to consciousness through virtual reality

Immersive virtual environments can break the deep, everyday connection between where our senses tell us we are and where we are actually located and whom we are with. The concept of 'presence' refers to the phenomenon of behaving and feeling as if we are in the virtual world created by computer displays. In this article, we argue that presence is worthy of study by neuroscientists, and that it might aid the study of perception and consciousness

Distribution and symmetrical patellofemoral pain patterns as revealed by high-resolution 3D body mapping:a cross-sectional study

Abstract Background Detailed pain mapping of extent and distribution in individuals with patellofemoral pain (PFP) within and around a complex structure such as the knee has yet to be explored. Methods Perceptions of on-going pain from adolescents and young adults (N = 35) with long-standing (>10 months) PFP were collected on high-resolution 3D digital body-schema of the knees. Location, area of pain, pain intensity, laterality, worse side of knee pain, symptom duration, and symmetry in bilateral knee pain were recorded. A threshold for naturally occurring variations in symmetrical knee pain drawings were collected from 18 healthy controls and used in combination with the development a symmetry index (0–1) to create a fuzzy rule for classifying symmetrical and non-symmetrical PFP patterns as compared to a PFP expert. The symmetry index was computed and tested using a correlation coefficient alone or in combination with the Jaccard index and the true and false positive rates (TPR and FPR, respectively) determined. Results The peripatellar region was the common report of pain location however, novel and nonconforming PFP patterns were identified and the majority of individuals (22 of 27) with bilateral PFP expressed highly-symmetric mirror-image pain. Individuals with symptom duration of 5 years or more had a greater area of pain, compared to those with symptoms for less than 5 years. The total area of pain was correlated to symptom duration for those with extended symptoms durations and a progression towards an “O” shaped pattern emerged. A TPR of 100% for identifying symmetrical knee pain patterns was found however the expert PFP tended to be stricter, as reflected in FPR of 20%. Conclusions A high proportion of PFP patterns or symptoms occur in mirrored locations and are exceptionally symmetrical, and long duration of symptoms appear to converge to an ‘O’ shape. Classifying symmetrical pain patterns is subjective however simple fuzzy rules and correlations can be used to increase objectivity. This study highlights a gap in knowledge of PFP symptom presentation, reveals what may be a natural progression of symptoms, and provides valuable clinical insight for both pain management and treatment

Treatment outcomes in HIV-infected adolescents attending a community-based antiretroviral therapy clinic in South Africa

<p>Abstract</p> <p>Background</p> <p>Very few data are available on treatment outcomes of adolescents living with HIV infection (whether perinatally acquired or sexually acquired) in sub-Saharan Africa. The present study therefore compared the treatment outcomes in adolescents with those of young adults at a public sector community-based ART programme in Cape Town, South Africa.</p> <p>Methods</p> <p>Treatment outcomes of adolescents (9-19 years) were compared with those of young adults (20-28 years), enrolled in a prospective cohort between September 2002 and June 2009. Kaplan-Meier estimates and Cox proportional hazard models were used to assess outcomes and determine associations with age, while adjusting for potential confounders. The treatment outcomes were mortality, loss to follow-up (LTFU), immunological response, virological suppression and virological failure.</p> <p>Results</p> <p>883 patients, including 65 adolescents (47 perinatally infected and 17 sexually infected) and 818 young adults, received ART. There was no difference in median baseline CD4 cell count between adolescents and young adults (133.5 vs 116 cells/μL; <it>p </it>= 0.31). Overall mortality rates in adolescents and young adults were 1.2 (0.3-4.8) and 3.1 (2.4-3.9) deaths per 100 person-years, respectively. Adolescents had lower rates of virological suppression (< 400 copies/mL) at 48 weeks (27.3% vs 63.1%; <it>p </it>< 0.001). Despite this, however, the median change in CD4 count from baseline at 48 weeks of ART was significantly greater for adolescents than young adults (373 vs 187 cells/μL; <it>p </it>= 0.0001). Treatment failure rates were 8.2 (4.6-14.4) and 5.0 (4.1-6.1) per 100 person-years in the two groups. In multivariate analyses, there was no significant difference in LTFU and mortality between age groups but increased risk in virological failure [AHR 2.06 (95% CI 1.11-3.81; <it>p </it>= 0.002)] in adolescents.</p> <p>Conclusions</p> <p>Despite lower virological suppression rates and higher rates of virological failure, immunological responses were nevertheless greater in adolescents than young adults whereas rates of mortality and LTFU were similar. Further studies to determine the reasons for poorer virological outcomes are needed.</p

Down-regulation of estrogen receptor-alpha and rearranged during transfection tyrosine kinase is associated with withaferin a-induced apoptosis in MCF-7 breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Withaferin A (WA), a naturally occurring withanolide, induces apoptosis in both estrogen-responsive MCF-7 and estrogen-independent MDA-MB-231 breast cancer cell lines with higher sensitivity in MCF-7 cells, but the underlying mechanisms are not well defined. The purpose of this study was to determine the anti-cancer effects of WA in MCF-7 breast cancer cells and explore alterations in estrogen receptor alpha (ERα) and its associated molecules <it>in vitro </it>as novel mechanisms of WA action.</p> <p>Methods</p> <p>The effects of WA on MCF-7 viability and proliferation were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and trypan blue exclusion assays. Apoptosis was evaluated by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry and Western blot analysis of poly (ADP-ribose) polymerase (PARP) cleavage. Cell cycle effects were analyzed by PI flow cytometry. Western blotting was also conducted to examine alterations in the expression of ERα and pathways that are associated with ERα function.</p> <p>Results</p> <p>WA resulted in growth inhibition and decreased viability in MCF-7 cells with an IC50 of 576 nM for 72 h. It also caused a dose- and time-dependent apoptosis and G2/M cell cycle arrest. WA-induced apoptosis was associated with down-regulation of ERα, REarranged during Transfection (RET) tyrosine kinase, and heat shock factor-1 (HSF1), as well as up-regulation of phosphorylated p38 mitogen-activated protein kinase (phospho-p38 MAPK), p53 and p21 protein expression. Co-treatment with protein synthesis inhibitor cycloheximide or proteasome inhibitor MG132 revealed that depletion of ERα by WA is post-translational, due to proteasome-dependent ERα degradation.</p> <p>Conclusions</p> <p>Taken together, down-regulation of ERα, RET, HSF1 and up-regulation of phospho-p38 MAPK, p53, p21 are involved in the pro-apoptotic and growth-inhibitory effects of WA in MCF-7 breast cancer cells <it>in vitro</it>. Down-regulation of ERα protein levels by WA is caused by proteasome-dependent ERα degradation.</p

Asymmetric recurrent laryngeal nerve conduction velocities and dorsal cricoarytenoid muscle electromyographic characteristics in clinically normal horses

The dorsal cricoarytenoid (DCA) muscles, are a fundamental component of the athletic horse’s respiratory system: as the sole abductors of the airways, they maintain the size of the rima glottis which is essential for enabling maximal air intake during intense exercise. Dysfunction of the DCA muscle leads to arytenoid collapse during exercise, resulting in poor performance. An electrodiagnostic study including electromyography of the dorsal cricoarytenoid muscles and conduction velocity testing of the innervating recurrent laryngeal nerves (RLn) was conducted in horses with normal laryngeal function. We detected reduced nerve conduction velocity of the left RLn, compared to the right, and pathologic spontaneous activity (PSA) of myoelectrical activity within the left DCA muscle in half of this horse population and the horses with the slowest nerve conduction velocities. The findings in this group of horses are consistent with left sided demyelination and axonal loss, consistent with Recurrent Laryngeal Neuropathy (RLN), a highly prevalent degenerative disorder of the RLn in horses that predominantly affects the left side. The detection of electromyographic changes compatible with RLN in clinically unaffected horses is consistent with previous studies that identified “subclinical” subjects, presenting normal laryngeal function despite neuropathologic changes within nerve and muscle confirmed histologically

Conserving Conflict? Transfrontier Conservation, Development Discourses and Local Conflict Between South Africa and Lesotho

This paper describes and analyses how discourses of conservation and development as well as migrant labour practices can be understood as transnational dynamics that both cement and complicate transnational relations. It also looks into how these dynamics articulate with, shape and are being shaped by ‘the local’. Focusing on the north-eastern boundary of Lesotho in the area of the ‘Maloti-Drakensberg transfrontier conservation and development project’, we show how conflictual situations put the ethnographic spotlight on the ways in which ‘local people’ in Lesotho deal with dual forces of localisation and transnationalisation. We argue that they accommodate, even appropriate, these dual pressures by adopting an increasingly flexible stance in terms of identity, alliances, livelihood options and discourses

Critical Early Roles for col27a1a and col27a1b in Zebrafish Notochord Morphogenesis, Vertebral Mineralization and Post-embryonic Axial Growth

Fibrillar collagens are well known for their links to human diseases, with which all have been associated except for the two most recently identified fibrillar collagens, type XXIV collagen and type XXVII collagen. To assess functions and potential disease phenotypes of type XXVII collagen, we examined its roles in zebrafish embryonic and post-embryonic development.We identified two type XXVII collagen genes in zebrafish, col27a1a and col27a1b. Both col27a1a and col27a1b were expressed in notochord and cartilage in the embryo and early larva. To determine sites of type XXVII collagen function, col27a1a and col27a1b were knocked down using morpholino antisense oligonucleotides. Knockdown of col27a1a singly or in conjunction with col27a1b resulted in curvature of the notochord at early stages and formation of scoliotic curves as well as dysmorphic vertebrae at later stages. These defects were accompanied by abnormal distributions of cells and protein localization in the notochord, as visualized by transmission electron microscopy, as well as delayed vertebral mineralization as detected histologically.Together, our findings indicate a key role for type XXVII collagen in notochord morphogenesis and axial skeletogenesis and suggest a possible human disease phenotype