Search

Supplemental Digital Content is available in the text.

IntroductionHaemorrhage causes most preventable prehospital trauma deaths and about a third of in-hospital trauma deaths. Tranexamic acid (TXA), administered soon after hospital arrival in certain trauma systems, is an effective therapy in preventing or managing acute traumatic coagulopathy. However, delayed administration of TXA appears to be ineffective or harmful. The effectiveness of prehospital TXA, incidence of thrombotic complications, benefit versus risk in advanced trauma systems and the mechanism of benefit remain uncertain.Methods and analysisThe Pre-hospital Anti-fibrinolytics for Traumatic Coagulopathy and Haemorrhage (The PATCH-Trauma study) is comparing TXA, initiated prehospital and continued in hospital over 8 hours, with placebo in patients with severe trauma at risk of acute traumatic coagulopathy. We present the trial protocol and an overview of the statistical analysis plan. There will be 1316 patients recruited by prehospital clinicians in Australia, New Zealand and Germany. The primary outcome will be the eight-level Glasgow Outcome Scale Extended (GOSE) at 6 months after injury, dichotomised to favourable (GOSE 5–8) and unfavourable (GOSE 1–4) outcomes, analysed using an intention-to-treat (ITT) approach. Secondary outcomes will include mortality at hospital discharge and at 6 months, blood product usage, quality of life and the incidence of predefined adverse events.Ethics and disseminationThe study was approved by The Alfred Hospital Research and Ethics Committee in Victoria and also approved in New South Wales, Queensland, South Australia, Tasmania and the Northern Territory. In New Zealand, Northern A Health and Disability Ethics Committee provided approval. In Germany, Witten/Herdecke University has provided ethics approval. The PATCH-Trauma study aims to provide definitive evidence of the effectiveness of prehospital TXA, when used in conjunction with current advanced trauma care, in improving outcomes after severe injury.Trial registration numberNCT02187120.

In this study, we demonstrate that methylation-dependent repression of the Pdha-2core promoter is mediated regionally through a consensus activating transcription factor/cAMP-responsive element-binding site located between nucleotides −54 and −62 upstream of the major transcriptional start site. Targeting of the CpG dinucleotide within thiscis-element significantly disrupts the ability of this basal promoter to activate gene expression in vitro and completely abolishes promoter activity in vivo. DNase I footprinting experiments indicated that availability of the nuclear factor(s) binding this element is limiting in sexually immature mouse testis, and as such, these factors may play an important role in the coordinate activation of early spermatogenic gene expression. Interestingly, CpG dinucleotides associated with the hypersensitive region flanking the activating transcription factor/cAMP-responsive element-binding site appear to confer some conformational structure on the promoter since mutations at these specific CpG dinucleotides result in elevated basal levels of transcription. This raises the possibility of a potential bifunctional role for CpG dinucleotides in either methylation-dependent or -independent processes. Our data support the notion that hypomethylation and transcription factor recruitment are necessary events that precede gene activation at the early stages of spermatogenesis.

Study Design. The presence or absence of rapidly centralizing, peripheralizing, or abolishing low back and radiating pain, as identified during a McKenzie mechanical lumbar assessment of patients with chronic lumbar pain, was compared prospectively with discographic pain provocation and anular competency. Objectives. To evaluate any relation between the responses of centralization and peripheralization with discogrophic findings. Summary of Background Data. Centralization of referred pain has been reported as a very common occurrence during McKenzie assessment and treatment. Patients whose pain centralizes have been shown to achieve superior treatment outcomes. A dynamic internal disc model has been hypothesized as an underlying mechanism for centralization that has not been studied previously. Methods. Pathients with chronically disabling low back pain who were referred for discography underwent preliminary blinded McKenzie clinical assessment and were categorized into three groups by their pain response. Patterns, or lack thereof, of pain response were then compared with blinded discographic pain provocation and anular findings. Results. During the McKenzie assessment, the referred pain of 50% centralized with 74% having positive discograms, of which 91% had an intact anulus. The pain of 25% peripheralized only (would not centralize); 69% of thes ehad positive discograms, but only 54% had an intact anulus. The distal pain of 25% did not respond at all, and only 12.5% of these had positive discograms. Conclusion. The McKenzie assessment process reliably differentiated discogenic from nondiscogenic pain (P

This article reports a prospective, randomized, multicentered study documenting changes in the intensity and location of low-back and referred pain to repeated end-range lumbar flexion and extension movements performed first while standing and then while recumbent during a single clinical patient evaluation. Significant and rapid changes in central and distal pain intensity and location of peripheral pain resulted from the performance of these movements. For the mean in both protocols, regardless of the order of spinal movements, end-range extension significantly decreased central and distal pain intensity and centralized referred pain. Flexion spinal movements, however, significantly increased mean central and distal pain intensity and peripheralized the pain. Forty percent of individual subjects had a clear preference for extension and 7% a clear preference for flexion.

Background Responses to public health need require information on the distribution of mental and physical ill health by demographic and socioeconomic factors at the local community level. Methods The South East London Community Health (SELCoH) study is a community psychiatric and physical morbidity survey. Trained interviewers conducted face-to-face computer assisted interviews with 1698 adults aged 16 years and over, from 1076 randomly selected private households in two south London boroughs. We compared the prevalence of common mental disorders, hazardous alcohol use, long standing illness and general physical health by demographic and socioeconomic indicators. Unadjusted and models adjusted for demographic and socioeconomic indicators are presented for all logistic regression models. Results Of those in the sample, 24.2% reported common mental disorder and 44.9% reported having a long standing illness, with 15.7% reporting hazardous alcohol consumption and 19.2% rating their health as fair or poor. The pattern of indicators identifying health inequalities for common mental disorder, poor general health and having a long term illness is similar; individuals who are socioeconomically disadvantaged have poorer health and physical health worsens as age increases for all groups. The prevalence of poor health outcomes by ethnic group suggests that there are important differences between groups, particularly for common mental disorder and poor general health. Higher socioeconomic status was protective for common mental disorder, fair or poor health and long standing illness, but those with higher socioeconomic status reported higher levels of hazardous alcohol use. The proportion of participants who met the criteria for common mental disorder with co-occurring functional limitations was similar or greater to those with poor physical health. Conclusions Health service providers and policy makers should prioritise high risk, socially defined groups in combating inequalities in individual and co-occurring poor mental and physical problems. In population terms, poor mental health has a similar or greater burden on functional impairment than long term conditions and perceived health.