Parasympathetic function is important in the induction and maintenance of sleep. We examined whether nocturnal vagal modulation of heart rate is related to the poor sleep quality commonly reported in chronic fatigue syndrome (CFS). Heart rate (HR, as R-R intervals) was continuously monitored during sleep in 20 patients with CFS and 20 matched control subjects. Questionnaires assessed demographic information, symptoms, functional impairment, and subjective sleep quality. CFS was associated with more sleep problems in general and poorer subjective sleep quality on the study night (all p < 0.003), and reports of repeated awakening during the night were 7 times more likely compared to healthy subjects (p = 0.017). Time and frequency-domain parameters of HR variability during sleep were significantly lower in patients with CFS (all p < 0.006). Multiple regression analyses revealed that heart rate variability (HRV) parameters were the best predictors of subjective sleep measures. This study identified significant reductions in vagal modulation of heart rate during sleep in CFS. Low HRV strongly predicted sleep quality-suggesting a pervasive state of nocturnal sympathetic hypervigilance in CFS.

The protease fibroblast activation protein (FAP) is a specific marker of activated mesenchymal cells in tumour stroma and fibrotic liver. A specific, reliable FAP enzyme assay has been lacking. FAP's unique and restricted cleavage of the post proline bond was exploited to generate a new specific substrate to quantify FAP enzyme activity. This sensitive assay detected no FAP activity in any tissue or fluid of FAP gene knockout mice, thus confirming assay specificity. Circulating FAP activity was ∼20- and 1.3-fold less in baboon than in mouse and human plasma, respectively. Serum and plasma contained comparable FAP activity. In mice, the highest levels of FAP activity were in uterus, pancreas, submaxillary gland and skin, whereas the lowest levels were in brain, prostate, leukocytes and testis. Baboon organs high in FAP activity included skin, epididymis, bladder, colon, adipose tissue, nerve and tongue. FAP activity was greatly elevated in tumours and associated lymph nodes and in fungal-infected skin of unhealthy baboons. FAP activity was 14- to 18-fold greater in cirrhotic than in non-diseased human liver, and circulating FAP activity was almost doubled in alcoholic cirrhosis. Parallel DPP4 measurements concorded with the literature, except for the novel finding of high DPP4 activity in bile. The new FAP enzyme assay is the first to be thoroughly characterised and shows that FAP activity is measurable in most organs and at high levels in some. This new assay is a robust tool for specific quantitation of FAP enzyme activity in both preclinical and clinical samples, particularly liver fibrosis.

We found no evidence of circadian rhythm disturbance in CFS. However, the role of autonomic activity in the experience of unrefreshing sleep warrants further assessment. The activity symptom-relationship modelled here is of clinical significance in the approach to activity and symptom management in the treatment of CFS.

BackgroundThe risk of alcohol‐related liver cirrhosis increases with increasing alcohol consumption, but many people with very high intake escape from liver disease. We postulate that susceptibility to alcoholic cirrhosis has a complex genetic component and propose that this can be dissected through a large and sufficiently powered genomewide association study (GWAS).MethodsThe GenomALC Consortium comprises researchers from Australia, France, Germany, Switzerland, United Kingdom, and United States, with a joint aim of exploring the genetic and genomic basis of alcoholic cirrhosis. For this National Institutes of Health/National Institute on Alcohol Abuse and Alcoholism funded study, we are recruiting high‐risk drinkers who are either cases (with alcoholic cirrhosis) or controls (drinking comparable amounts over similar time, but free of significant liver disease). Extensive phenotypic data are obtained using semistructured interviews and patient records, and blood samples are collected.ResultsWe have successfully recruited 859 participants including 538 matched case–control samples as of September 2014, using study‐specific inclusion–exclusion criteria and data collection protocols. Of these, 580 are cases (442 men and 138 women) and 279 are controls (205 men and 74 women). Duration of excessive drinking was slightly greater in cases than controls and was significantly less in women than men. Cases had significantly lower lifetime alcohol intake than controls. Both cases and controls had a high prevalence of reported parental alcohol problems, but cases were significantly more likely to report that a father with alcohol problems had died from liver disease (odds ratio 2.53, 95% confidence interval 1.31 to 4.87, p = 0.0055).ConclusionsRecruitment of participants for a GWAS of alcoholic cirrhosis has proved feasible across countries with multiple sites. Affected patients often consume less alcohol than unaffected ones, emphasizing the existence of individual vulnerability factors. Cases are more likely to report liver disease in a father with alcohol problems than controls, consistent with a potential genetic component to the risk of alcoholic cirrhosis.

Liver disease is the greatest cause of death related to alcohol and a major public health problem. While excessive alcohol intake results in hepatosteatosis in most individuals, this can progress in some to more severe forms of liver disease including fibrosis and cirrhosis. An ongoing challenge in the management of alcoholic liver disease is the identification of liver injury early in the disease process such that intervention strategies can prevent serious long term outcomes. Given that excessive alcohol consumption results in dysregulation of lipid metabolism we applied lipid profiling technology to characterise and compare serum lipid profiles from excessive chronic drinkers with no liver disease to those with advanced alcoholic cirrhosis. In a cohort of 59 excessive drinkers (31 with liver cirrhosis and 28 with no evidence of liver disease) we used electrospray ionisation tandem mass spectrometry to measure over 300 individual lipid species in serum, including species of the major phospholipid, sphingolipid, glycerolipid and sterol classes. Six of the 25 lipid classes and subclasses were significantly associated with alcoholic liver cirrhosis; these included dihexosylceramide, trihexosylceramide, alkylphosphatidylcholine, lysoalkylphosphatidylcholine, phosphatidylinositol and free cholesterol. Multivariate classification models created with only clinical characteristics gave an optimal model with an AUC of 0.847 and an accuracy of 79.7%. The addition of lipid measurements to the clinical characteristics resulted in models of improved performance with an AUC of 0.892 and accuracy of 81.8%. The gain in AUC and accuracy of the combined models highlight the potential of serum lipids as markers of liver injury in alcoholic liver disease.

Hematology and serum chemistry values were obtained from 28 male and 22 female stray dogs in Chittagong Metropolitan area, Bangladesh. The goal of the study was to establish reference value for hematology and serum chemistry for these semi wild animals in relation to age, sex, reproductive stage and body condition. No significant differences were found for mean values of hemoglobin, packed cell volume, mean corpuscular hemoglobin concentration, white blood cell, differential leukocyte count, total protein, albumin, glucose, cholesterol, phosphorus and potassium among or between sexes, ages, reproductive states or body conditions. Significant differences were noted for erythrocyte sedimentation rate (p<0.02) between sexes. Among different age groups significant differences were found for total red blood cell count (p<0.001). Different body conditions have significant differences in red blood cell count, mean corpuscular volume and mean corpuscular hemoglobin (p<0.001). Pregnant and non-pregnant females differed significantly in their red blood cell count, mean corpuscular volume and mean corpuscular hemoglobin (p<0.001).

ObjectiveTo examine the characteristics of frequent visitors (FVs) to emergency departments (EDs) and develop a predictive model to identify those with high risk of a future representations to ED among younger and general population (aged ≤70 years).Design and settingA retrospective analysis of ED data targeting younger and general patients (aged ≤70 years) were collected between 1 January 2009 and 30 June 2016 from a public hospital in Australia.ParticipantsA total of 343 014 ED presentations were identified from 170 134 individual patients.Main outcome measuresProportion of FVs (those attending four or more times annually), demographic characteristics (age, sex, indigenous and marital status), mode of separation (eg, admitted to ward), triage categories, time of arrival to ED, referral on departure and clinical conditions. Statistical estimates using a mixed-effects model to develop a risk predictive scoring system.ResultsThe FVs were characterised by young adulthood (32.53%) to late-middle (26.07%) aged patients with a higher proportion of indigenous (5.7%) and mental health-related presentations (10.92%). They were also more likely to arrive by ambulance (36.95%) and leave at own risk without completing their treatments (9.8%). They were also highly associated with socially disadvantage groups such as people who have been divorced, widowed or separated (12.81%). These findings were then used for the development of a predictive model to identify potential FVs. The performance of our derived risk predictive model was favourable with an area under the receiver operating characteristic (ie, C-statistic) of 65.7%.ConclusionThe development of a demographic and clinical profile of FVs coupled with the use of predictive model can highlight the gaps in interventions and identify new opportunities for better health outcome and planning.

Introduction: Growing pressures upon Emergency Departments [ED] call for new ways of working with frequent presenters who, although small in number, place extensive demands on services, to say nothing of the costs and consequences for the patients themselves. EDs are often poorly equipped to address the multi-dimensional nature of patient need and the complex circumstances surrounding repeated presentation. Employing a model of intensive short-term community-based case management, the Checkpoint program sought to improve care coordination for this patient group, thereby reducing their reliance on ED.Method: This study employed a single group interrupted time series design, evaluating patient engagement with the program and year-on-year individual differences in the number of ED visits pre and post enrolment. Associated savings were also estimated.Results: Prior to intervention, there were two dominant modes in the ED presentation trends of patients. One group had a steady pattern with ≥7 presentations in each of the last four years. The other group had an increasing trend in presentations, peaking in the 12 months immediately preceding enrolment. Following the intervention, both groups demonstrated two consecutive year-on-year reductions. By the second year, and from an overall peak of 22.5 presentations per patient per annum, there was a 53% reduction in presentations. This yielded approximate savings of $7100 per patient.Discussion: Efforts to improve care coordination, when combined with proactive case management in the community, can impact positively on ED re-presentation rates, provided they are concerted, sufficiently intensive and embed the principles of integration. Conclusion:The Checkpoint program demonstrated sufficient promise to warrant further exploration of its sustainability. However, health services have yet to determine the ideal organisational structures and funding arrangements to support such initiatives.