Cold-induced vasoconstriction at forearm and hand skin sites: the effect of age

During mild cold exposure, elderly are at risk of hypothermia. In humans, glabrous skin at the hands is well adapted as a heat exchanger. Evidence exists that elderly show equal vasoconstriction due to local cooling at the ventral forearm, yet no age effects on vasoconstriction at hand skin have been studied. Here, we tested the hypotheses that at hand sites (a) elderly show equal vasoconstriction due to local cooling and (b) elderly show reduced response to noradrenergic stimuli. Skin perfusion and mean arterial pressure were measured in 16 young adults (Y: 18–28 years) and 16 elderly (E: 68–78 years). To study the effect of local vasoconstriction mechanisms local sympathetic nerve terminals were blocked by bretylium (BR). Baseline local skin temperature was clamped at 33°C. Next, local temperature was reduced to 24°C. After 15 min of local cooling, noradrenalin (NA) was administered to study the effect of neural vasoconstriction mechanisms. No significant age effect was observed in vasoconstriction due to local cooling at BR sites. After NA, vasoconstriction at the forearm showed a significant age effect; however, no significant age effect was found at the hand sites. [Change in CVC (% from baseline): Forearm Y: −76 ± 3 vs. E: −60 ± 5 (P < 0.01), dorsal hand Y: −74 ± 4 vs. E: −72 ± 4 (n.s.), ventral hand Y: −80 ± 7 vs. E: −70 ± 11 (n.s.)]. In conclusion, in contrast to results from the ventral forearm, elderly did not show a blunted response to local cooling and noradrenalin at hand skin sites. This indicates that at hand skin the noradrenergic mechanism of vasoconstriction is maintained with age

Vascular responses of the extremities to transdermal application of vasoactive agents in Caucasian and African descent individuals

This is an accepted manuscript of an article published by Springer in European Journal of Applied Physiology on 04/04/2015, available online: https://doi.org/10.1007/s00421-015-3164-2 The accepted version of the publication may differ from the final published version.© 2015, Springer-Verlag Berlin Heidelberg. Purpose: Individuals of African descent (AFD) are more susceptible to non-freezing cold injury than Caucasians (CAU) which may be due, in part, to differences in the control of skin blood flow. We investigated the skin blood flow responses to transdermal application of vasoactive agents. Methods: Twenty-four young males (12 CAU and 12 AFD) undertook three tests in which iontophoresis was used to apply acetylcholine (ACh 1 w/v %), sodium nitroprusside (SNP 0.01 w/v %) and noradrenaline (NA 0.5 mM) to the skin. The skin sites tested were: volar forearm, non-glabrous finger and toe, and glabrous finger (pad) and toe (pad). Results: In response to SNP on the forearm, AFD had less vasodilatation for a given current application than CAU (P = 0.027–0.004). ACh evoked less vasodilatation in AFD for a given application current in the non-glabrous finger and toe compared with CAU (P = 0.043–0.014) with a lower maximum vasodilatation in the non-glabrous finger (median [interquartile], AFD n = 11, 41[234] %, CAU n = 12, 351[451] %, P = 0.011) and non-glabrous toe (median [interquartile], AFD n = 9, 116[318] %, CAU n = 12, 484[720] %, P = 0.018). ACh and SNP did not elicit vasodilatation in the glabrous skin sites of either group. There were no ethnic differences in response to NA. Conclusion: AFD have an attenuated endothelium-dependent vasodilatation in non-glabrous sites of the fingers and toes compared with CAU. This may contribute to lower skin temperature following cold exposure and the increased risk of cold injuries experienced by AFD.Published versio

Protocol for the ProFHER (PROximal Fracture of the Humerus: Evaluation by Randomisation) trial: a pragmatic multi-centre randomised controlled trial of surgical versus non-surgical treatment for proximal fracture of the humerus in adults

<p>Abstract</p> <p>Background</p> <p>Proximal humeral fractures, which occur mainly in older adults, account for approximately 4 to 5% of all fractures. Approximately 40% of these fractures are displaced fractures involving the surgical neck. Management of this group of fractures is often challenging and the outcome is frequently unsatisfactory. In particular it is not clear whether surgery gives better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform this decision.</p> <p>Methods/Design</p> <p>We aim to undertake a pragmatic UK-based multi-centre randomised controlled trial evaluating the effectiveness and cost-effectiveness of surgical versus standard non-surgical treatment for adults with an acute closed displaced fracture of the proximal humerus with involvement of the surgical neck. The choice of surgical intervention is left to the surgeon, who must use techniques that they are fully experienced with. This will avoid 'learning curve' problems. We will promote good standards of non-surgical care, similarly insisting on care-provider competence, and emphasize the need for comparable provision of rehabilitation for both groups of patients.</p> <p>We aim to recruit 250 patients from a minimum of 18 NHS trauma centres throughout the UK. These patients will be followed-up for 2 years. The primary outcome is the Oxford Shoulder Score, which will be collected via questionnaires completed by the trial participants at 6, 12 and 24 months. This is a 12-item condition-specific questionnaire providing a total score based on the person's subjective assessment of pain and activities of daily living impairment. We will also collect data for other outcomes, including general health measures and complications, and for an economic evaluation. Additionally, we plan a systematic collection of reasons for non-inclusion of eligible patients who were not recruited into the trial, and their baseline characteristics, treatment preferences and intended treatment.</p> <p>Discussion</p> <p>This article presents the protocol for a multi-centre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN50850043</p

A 2x2 randomised factorial SWAT of the use of a pen and small, financial incentive to improve recruitment in a randomised controlled trial of yoga for older adults with multimorbidity [version 2; peer review: 2 approved]

Background: Monetary and other incentives may increase recruitment to randomised controlled trials. Methods: 2x2 factorial ‘study within a trial’ of including a pen and/or £5 (GBP) in cash with a postal recruitment pack to increase the number of participants randomised into the host trial (‘Gentle Years Yoga’) for older adults with multimorbidity. Secondary outcomes: return, and time to return, of screening form, and the cost per additional participant randomised. Binary data were analysed using logistic regression and time to return using Cox proportional hazards regression. Results: 818 potential host trial participants were included. Between those sent a pen (n=409) and not sent a pen (n=409), there was no evidence of a difference in the proportion of participants randomised (15 (3.7%) versus 11 (2.7%); OR 1.38, 95% CI 0.63–3.04), in returning a screening form (66 (16.1%) versus 61 (14.9%); OR 1.10, 95% CI 0.75–1.61) nor in time to return the screening form (HR 1.09, 95% CI 0.77–1.55). Between those sent £5 (n=409) and not sent £5 (n=409), there was no evidence of increased randomisation (14 (3.4%) versus 12 (2.9%); OR 1.18, 95% CI 0.54–2.57), but more screening forms were returned (77 (18.8%) versus 50 (12.2%); OR 1.67, 95% CI 1.13–2.45) and there was decreased time to return screening form (HR 1.56, 95% CI 1.09–2.22). No significant interaction between the interventions was observed. The cost per additional participant randomised was £32 and £1000 for the pen and £5, respectively. Conclusion: A small, monetary incentive did not result in more participants being randomised into the host trial but did encourage increased and faster response to the recruitment invitation. Since it is relatively costly, we do not recommend this intervention for use to increase recruitment in this population. Pens were cheaper but did not provide evidence of benefit

The HIM (Health for Izhevsk Men) trial protocol

BACKGROUND: Russia is one of the very few industrialised countries in the world where life expectancy has been declining. Alcohol has been implicated as a major contributor to the rapid fluctuations observed in male life expectancy since 1985 that have been particularly marked among working-age men. One approach to reducing the alcohol problem in Russia is 'brief interventions' which seek to change views of the personal acceptability of excessive drinking and to encourage self-directed behaviour change. There is limited understanding in Russia of the salience and applicability of Motivational Interviewing (MI), a well-defined brief intervention commonly used to target alcohol-related behaviour, but MI may have important potential for success within the Russian context. METHODS/DESIGN: The study will be an individually randomised two-armed parallel group exploratory trial. The primary hypothesis is that a brief adaptation of MI will be effective in reducing self-reported hazardous drinking at 3 months. The secondary hypothesis is that it will be effective in reducing self-reported past week beverage alcohol consumption, alcohol dependence and related problems at 3 months and at 12 months. MI will also be effective at 12 months in reducing self-reported hazardous drinking, alcohol dependence and related problems, proxy reported hazardous drinking, and recent alcohol use as indicated by bio-markers. Participants are drawn from the Izhevsk Family Study II, with eligibility determined based on proxy reports of hazardous drinking in the past year. All participants undergo a health check, with MI subsequently delivered to those in the intervention arm. Signed consent is obtained from those in the intervention arm at this point. Both groups are then invited for 3 and 12 month follow ups. The control group will not receive any additional intervention. TRIAL REGISTRATION: ISRCTN82405938

Clinical Value of Prognostic Instruments to Identify Patients with an Increased Risk for Osteoporotic Fractures: Systematic Review

There is a plethora of evidence available studying the association of risk profiles and the development of osteoporotic fractures. The small number of out-of-sample validations, the large variety of study characteristics, outcomes and follow-up periods impedes from deriving robust summaries and from conclusions regarding the clinical performance of many tools. First and foremost, future activity in this field should aim at reaching a consensus among clinical experts in respect to the existing instruments. Then we call for careful validations and expedient adaptations for local circumstances of the most promising candidates

Coevolution of Interacting Fertilization Proteins

Reproductive proteins are among the fastest evolving in the proteome, often due to the consequences of positive selection, and their rapid evolution is frequently attributed to a coevolutionary process between interacting female and male proteins. Such a process could leave characteristic signatures at coevolving genes. One signature of coevolution, predicted by sexual selection theory, is an association of alleles between the two genes. Another predicted signature is a correlation of evolutionary rates during divergence due to compensatory evolution. We studied female–male coevolution in the abalone by resequencing sperm lysin and its interacting egg coat protein, VERL, in populations of two species. As predicted, we found intergenic linkage disequilibrium between lysin and VERL, despite our demonstration that they are not physically linked. This finding supports a central prediction of sexual selection using actual genotypes, that of an association between a male trait and its female preference locus. We also created a novel likelihood method to show that lysin and VERL have experienced correlated rates of evolution. These two signatures of coevolution can provide statistical rigor to hypotheses of coevolution and could be exploited for identifying coevolving proteins a priori. We also present polymorphism-based evidence for positive selection and implicate recent selective events at the specific structural regions of lysin and VERL responsible for their species-specific interaction. Finally, we observed deep subdivision between VERL alleles in one species, which matches a theoretical prediction of sexual conflict. Thus, abalone fertilization proteins illustrate how coevolution can lead to reproductive barriers and potentially drive speciation

Theoretical framework and methodological development of common subjective health outcome measures in osteoarthritis: a critical review

Subjective measures involving clinician ratings or patient self-assessments have become recognised as an important tool for the assessment of health outcome. The value of a health outcome measure is usually assessed by a psychometric evaluation of its reliability, validity and responsiveness. However, psychometric testing involves an accumulation of evidence and has recognised limitations. It has been suggested that an evaluation of how well a measure has been developed would be a useful additional criteria in assessing the value of a measure. This paper explored the theoretical background and methodological development of subjective health status measures commonly used in osteoarthritis research. Fourteen subjective health outcome measures commonly used in osteoarthritis research were examined. Each measure was explored on the basis of their i) theoretical framework (was there a definition of what was being assessed and was it part of a theoretical model?) and ii) methodological development (what was the scaling strategy, how were the items generated and reduced, what was the response format and what was the scoring method?). Only the AIMS, SF-36 and WHOQOL defined what they were assessing (i.e. the construct of interest) and no measure assessed was part of a theoretical model. None of the clinician report measures appeared to have implemented a scaling procedure or described the rationale for the items selected or scoring system. Of the patient self-report measures, the AIMS, MPQ, OXFORD, SF-36, WHOQOL and WOMAC appeared to follow a standard psychometric scaling method. The DRP and EuroQol used alternative scaling methods. The review highlighted the general lack of theoretical framework for both clinician report and patient self-report measures. This review also drew attention to the wide variation in the methodological development of commonly used measures in OA. While, in general the patient self-report measures had good methodological development, the clinician report measures appeared less well developed. It would be of value if new measures defined the construct of interest and, that the construct, be part of theoretical model. By ensuring measures are both theoretically and empirically valid then improvements in subjective health outcome measures should be possible