Depression, anxiety, substance misuse and self-harm in children and young people with rare chronic liver disease

The burden of mental illness in young people with chronic liver disease is not known. In this population cohort study in England, we identified 358 individuals (aged ≤25 years) diagnosed with autoimmune hepatitis or liver disease related to cystic fibrosis and 1541 propensity-score-matched controls. By the first year of follow-up, the cumulative burden of psychiatric events in participants with liver disease was high compared with controls: anxiety disorder (6.87 per 100 individuals [95% CI 4.00-9.73] v. 2.22 [95% CI 1.37-3.07]), depression (5.10 [95% CI 2.83-7.37] v. 0.86 [95% CI 0.53-1.19]), substance misuse (10.61 [95% CI 9.50-11.73] v. 1.23 [95% CI 0.71-1.75]) and self-harm (3.09 [95% CI 1.12-5.05] v. 0.20 [95% CI 0.07-0.33]). Participants with liver disease had a 2-fold increase (OR = 1.94, 95% CI 1.45-2.58), a 2.5-fold increase (OR = 2.59, 95% CI 1.91-3.50) and 4.4-fold increase (OR = 4.44; 95% CI 3.46-5.71) in the risk of anxiety, depression and substance misuse, respectively. These findings highlight the need for effective intervention in psychiatric disorders in young people with rare liver disease

Coagulation profiles are associated with early clinical outcomes in neonatal encephalopathy

Introduction: Neonatal encephalopathy (NE) is associated with coagulation abnormalities. We aimed to investigate the serial alterations in coagulation profiles in term infants with NE and correlate with their clinical outcomes. This was a prospective cohort study in a tertiary referral, university-affiliated maternity hospital. Neonates exposed to perinatal asphyxia were recruited (n = 82) and 39 received therapeutic hypothermia. Infants had serial coagulation tests including platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen in the first week of life. The main outcome measures included MRI brain and EEG seizures. Our results show that mortality was predicted on day 1 by decreased Fibrinogen (AUC = 0.95, p = 0.009) and by PT on day 2 with a cutoff of 22 s. An abnormal MRI was predicted by Fibrinogen on day 3 with a cut-off value of 2 g/L. For prediction of grade II/III NE, PT on day 2 of life was strongest with a cut-off value of 14 s. Only elevated APTT levels on day 1 of life were predictive of seizures (AUC = 0.65, p = 0.04). Conclusion: Coagulation parameters are strong predictors of outcomes such as abnormal NE grade, seizures, and mortality

Sensitivity to Sunburn Is Associated with Susceptibility to Ultraviolet Radiation–Induced Suppression of Cutaneous Cell–Mediated Immunity

Skin cancer incidence is highest in white-skinned people. Within this group, skin types I/II (sun sensitive/tan poorly) are at greater risk than skin types III/IV (sun tolerant/tan well). Studies in mice demonstrate that ultraviolet radiation (UVR)-induced suppression of cell-mediated immune function plays an important role in the development of skin cancer and induces a susceptibility to infectious disease. A similar role is suspected in humans, but we lack quantitative human data to make risk assessments of ambient solar exposure on human health. This study demonstrates that ambient levels of solar UVR, typically experienced within 1 h of exposure to noonday summer sunlight, can suppress contact hypersensitivity (CHS) responses in healthy white-skinned humans in vivo (n = 93). There was a linear relationship between increase in erythema and suppression of CHS (P < 0.001), and a moderate sunburn (two minimal erythema doses [2 MED]) was sufficient to suppress CHS in all volunteers by 93%. However, a single suberythemal exposure of either 0.25 or 0.5 MED suppressed CHS responses by 50 and 80%, respectively, in skin types I/II, whereas 1 MED only suppressed CHS by 40% in skin types III/IV. The two- to threefold greater sensitivity of skin types I/II for a given level of sunburn may play a role in their greater sensitivity to skin cancer

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Physiotherapy for sleep disturbance in chronic low back pain: a feasibility randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>Sleep disturbance is becoming increasingly recognised as a clinically important symptom in people with chronic low back pain (CLBP, low back pain >12 weeks), associated with physical inactivity and depression. Current research and international clinical guidelines recommend people with CLBP assume a physically active role in their recovery to prevent chronicity, but the high prevalence of sleep disturbance in this population may be unknowingly limiting their ability to participate in exercise-based rehabilitation programmes and contributing to poor outcomes. There is currently no knowledge concerning the effectiveness of physiotherapy on sleep disturbance in people with chronic low back pain and no evidence of the feasibility of conducting randomized controlled trials that comprehensively evaluate sleep as an outcome measure in this population.</p> <p>Methods/Design</p> <p>This study will evaluate the feasibility of a randomised controlled trial (RCT), exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain. A presenting sample of 60 consenting patients will be recruited in the physiotherapy department of Beaumont Hospital, Dublin, Ireland, and randomly allocated to one of the three groups in a concealed manner. The main outcomes will be sleep quality (self-report and objective measurement), and self-reported functional disability, pain, quality of life, fear avoidance, anxiety and depression, physical activity, and patient satisfaction. Outcome will be evaluated at baseline, 3 months and 6 months. Qualitative telephone interviews will be embedded in the research design to obtain feedback from a sample of participants' about their experiences of sleep monitoring, trial participation and interventions, and to inform the design of a fully powered future RCT. Planned analysis will explore trends in the data, effect sizes and clinically important effects (quantitative data), and thematic analysis (qualitative data).</p> <p>Discussion</p> <p>This study will evaluate the feasibility of a randomised controlled trial exploring the effects of three forms of physiotherapy (supervised general exercise programme, individualized walking programme and usual physiotherapy, which will serve as the control group) on sleep quality in people with chronic low back pain.</p> <p>Trial Registration</p> <p>Current controlled trial ISRCTN54009836</p

A combination of mutations in AKR1D1 and SKIV2L in a family with severe infantile liver disease.

Infantile cholestatic diseases can be caused by mutations in a number of genes involved in different hepatocyte molecular pathways. Whilst some of the essential pathways have a well understood function, such as bile biosynthesis and transport, the role of the others is not known. Here we report the findings of a clinical, biochemical and molecular study of a family with three patients affected with a severe infantile cholestatic disease. A novel homozygous frameshift germline mutation (c.587delG) in the AKR1D1 gene; which encodes the enzyme Δ 4-3-oxosteroid 5β-reductase that is required for synthesis of primary bile acids and is crucial for establishment of normal bile flow, was found in all 3 patients. Although the initial bile acid analysis was inconclusive, subsequent testing confirmed the diagnosis of a bile acid biogenesis disorder. An additional novel homozygous frameshift mutation (c.3391delC) was detected in SKIV2L in one of the patients. SKIV2L encodes a homologue of a yeast ski2 protein proposed to be involved in RNA processing and mutations in SKIV2L were recently described in patients with Tricohepatoenteric syndrome (THES). A combination of autozygosity mapping and whole-exome-sequencing allowed the identification of causal mutations in this family with a complex liver phenotype. Although the initial 2 affected cousins died in the first year of life, accurate diagnosis and management of the youngest patient led to successful treatment of the liver disease and disease-free survival.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

The Samurai Project: verifying the consistency of black-hole-binary waveforms for gravitational-wave detection

We quantify the consistency of numerical-relativity black-hole-binary waveforms for use in gravitational-wave (GW) searches with current and planned ground-based detectors. We compare previously published results for the $(\ell=2,| m | =2)$ mode of the gravitational waves from an equal-mass nonspinning binary, calculated by five numerical codes. We focus on the 1000M (about six orbits, or 12 GW cycles) before the peak of the GW amplitude and the subsequent ringdown. We find that the phase and amplitude agree within each code's uncertainty estimates. The mismatch between the $(\ell=2,| m| =2)$ modes is better than $10^{-3}$ for binary masses above $60 M_{\odot}$ with respect to the Enhanced LIGO detector noise curve, and for masses above $180 M_{\odot}$ with respect to Advanced LIGO, Virgo and Advanced Virgo. Between the waveforms with the best agreement, the mismatch is below $2 \times 10^{-4}$. We find that the waveforms would be indistinguishable in all ground-based detectors (and for the masses we consider) if detected with a signal-to-noise ratio of less than $\approx14$, or less than $\approx25$ in the best cases.Comment: 17 pages, 9 figures. Version accepted by PR