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Introduction: Shielding aimed to protect those predicted to be at highest risk from COVID-19 and was uniquely implemented in the UK during the COVID-19 pandemic. Clinically extremely vulnerable people identified through algorithms and screening of routine National Health Service (NHS) data were individually and strongly advised to stay at home and strictly self-isolate even from others in their household. This study will generate a logic model of the intervention and evaluate the effects and costs of shielding to inform policy development and delivery during future pandemics., Methods and Analysis: This is a quasiexperimental study undertaken in Wales where records for people who were identified for shielding were already anonymously linked into integrated data systems for public health decision-making. We will: interview policy-makers to understand rationale for shielding advice to inform analysis and interpretation of results; use anonymised individual-level data to select people identified for shielding advice in March 2020 and a matched cohort, from routine electronic health data sources, to compare outcomes; survey a stratified random sample of each group about activities and quality of life at 12 months; use routine and newly collected blood data to assess immunity; interview people who were identified for shielding and their carers and NHS staff who delivered healthcare during shielding, to explore compliance and experiences; collect healthcare resource use data to calculate implementation costs and cost-consequences. Our team includes people who were shielding, who used their experience to help design and deliver this study., Ethics and Dissemination: The study has received approval from the Newcastle North Tyneside 2 Research Ethics Committee (IRAS 295050). We will disseminate results directly to UK government policy-makers, publish in peer-reviewed journals, present at scientific and policy conferences and share accessible summaries of results online and through public and patient networks., Competing Interests: Competing interests: RL, SJ, AJ and AE are members of the Welsh Government COVID-19 Technical Advisory Group. AJ is also co-chair of the Scientific Pandemic Insights Group on Behaviours, which is a subgroup of the Scientific Advisory Group for Emergencies advising the UK government. SJ is also a member of the Welsh Government Testing Technical Advisory Group and Cardiff University COVID Strategic Advisory Board., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Public Health England (PHE) aims meet the WHO target to eliminate hepatitis C as a public health concern by 2030. One aspect of this strategy is to use historical surveillance data of anti -HCV positive patients identified by PHE to re-engage with offers of PCR testing and treatment if RNA-positive. Operational Delivery Networks (ODN), who deliver Hepatitis C treatment across 22 regions in England, are responsible for enacting this initiative. This study aims to evaluate the effectiveness of using this data with regional PCR results to re-engage HCV-infected persons in the West Midlands region of England., Study Design: A longitudinal prospective study using historical surveillance data., Methods: A dataset of historical anti -HCV positive antibody patients provided to the ODN by PHE was cross-referenced with HCV RNA data from 01/01/1996 to 01/01/2019 from five laboratories across the West Midlands. Letters were sent to the general practitioner and to the patients who were HCV RNA positive to invite them for repeat testing and treatment to achieve cure., Results: From a dataset of 4540 anti -HCV antibody results, 31.7% (n=1440) had a PCR result: 48.1% (n=693) were PCR positive for HCV RNA. 693 letters were sent to GPs with responses from 14.2% (n=99). By May 2021, only 212 patient letters were sent (due to significant interruption by the COVID-19 pandemic) and 11.3% (n=24) replied, 17 presented for PCR testing and 4 were found to be viraemic. To date, one patient has achieved cure and three have completed treatment awaiting confirmation of cure., Conclusion: The use of historical anti -HCV antibody results can be used to successfully re-engage people into testing and treatment for hepatitis C, albeit with modest gains., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier Ltd on behalf of The Royal Society for Public Health.)

Background & Aims: The role of liver transplantation (LT) for the relief of fatigue in patients with primary biliary cirrhosis (PBC) is unclear, and while many centers exclude fatigue as an indication for transplantation, there have been no studies to prospectively evaluate the impact of LT on fatigue. We aimed at assessing the severity of fatigue in LT candidates with PBC and the impact of LT on fatigue., Methods: In a prospective, longitudinal study, we used the PBC-40 questionnaire in 49 adult patients with PBC at listing and at 6, 12, and 24 months after LT and in two sex- and age-matched cohorts of community controls and non-transplanted PBC patients. Correlation analysis was used to assess the relationship between liver function and fatigue. ANOVA was used to compare the variation of fatigue score before and after LT., Results: There was no correlation between MELD and fatigue before LT (r(2)=0.01). Overall, the fatigue score after LT was substantially lower than before LT, falling from 40.7 ± 11.4 pre-transplant to 27.7 ± 9.5, 28.7 ± 10.1, 26.2 ± 10.1 (p<0.0001) at 6, 12, and 24 months after LT, respectively. The same improvement of fatigue was observed in both low-MELD (<17) and high-MELD (≥ 17) patients. Improvement in fatigue was also evident in the comparison with a "non-transplant PBC" control group (31.1 ± 11.6, p=0.03). However, 44% of the total cohort, and 47% of those with low-MELD, for whom the probability of dying of LT may be higher than that of dying without LT, had moderate to severe fatigue (defined as a fatigue score ≥ 29) at two years after LT. Moreover, fatigue scores at two years were higher in the transplant PBC cohort compared to a cohort of community controls (17.8 ± 5.9, p<0.0001)., Conclusions: Liver transplantation is associated with improvement in fatigue in patients with PBC. However, a substantial proportion of patients continue to suffer from significant fatigue after two years. Whether the improvement is enough to justify organ allocation in patients with fatigue alone, without liver failure, is still an open issue. Certainly, in the era of organ shortage, with many patients dying waiting for a graft, this may not represent the optimal use of donated deceased organs., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Epithelioid hemangioendothelioma is a rare soft-tissue tumor with unpredictable malignant potential. This type of tumor can occur in the liver but is very rare. Signs and symptoms are often nonspecific, and even if the problem is not misdiagnosed, arriving at a clear diagnosis can take some time. This article describes 3 patients who had very different signs and symptoms, all of whom were referred to a specialist center for liver transplantation in 1 year. All 3 patients proceeded to transplantation and made a good recovery. They have regular follow-up at the transplant center, and to date, no recurrence of hepatic epithelioid hemangioendothelioma has been seen in these 3 patients.

The Modern Matron was introduced into hospital Trusts in April 2002 to improve the basics of patient care. They were to be easily identifiable, highly visible and authoritative figures. This article reports on a quantitative study done to ascertain if patients can identify the Modern Matron in one acute NHS Trust. A researcher-developed questionnaire was sent to 20 Modern Matrons and a different questionnaire was distributed to 72 randomly selected patients. The results demonstrated that only 5% of patients surveyed were able to correctly identify the Modern Matron by their uniform. This may be explained by the response from the Modern Matrons when asked how much time was spent with patients; 67% of their normal working day was taken up with management of staff, paperwork and meetings, leaving very little direct patient time.

Educating family members of transplant recipients has long been recognized as an important factor in preparation for organ transplantation. This preparation may help the family come to terms with potential complications, the possibility of extended hospitalization, and the psychological changes that their loved ones might experience. Although education of a spouse or essential others may take place, children of an organ recipient may be unintentionally overlooked in the teaching process. This article describes how an educational booklet for children of adults undergoing liver transplantaion was developed and introduced into a liver transplant unit.

Dorsal root ganglion (DRG) neurons that mediate nociception express the high affinity NGF receptor (trkA) gene and the preprotachykinin (PPT) gene. NGF has been shown to regulate both of these DRG neuronal genes. Our laboratory has shown that these genes are also regulated by estrogen. Long-term daily estrogen replacement, in adult ovariectomized (OVX) rats, causes a coordinate decline in trkA and beta-PPT mRNA levels in lumbar DRG neurons, while short-term estrogen replacement increases trkA mRNA levels in uninjured as well as in axotomized lumbar DRG neurons. The purpose of the current study was to test the hypothesis that short-term estrogen replacement increases DRG beta-PPT mRNA levels in lumbar DRG neurons of OVX rats and that the increase is dependent on target-derived NGF. Sciatic nerve transection (SNT) was used to eliminate target-derived NGF in L4 and L5 DRGs in adult OVX rats. Seven days later, one-half of the SNT and one-half of the animals that had received sham sciatic nerve transactions (SHAM) received two daily injections of estradiol benzoate (EB). The remaining rats received two daily injections of vehicle alone. Quantitative in situ hybridization analyses of sections from L4 and L5 DRGs showed that two daily injections of EB significantly increased beta-PPT mRNA levels in DRGs of SHAM animals, but had no effect on beta-PPT mRNA levels in DRGs from SNT animals. These data coupled with our earlier observations of the effect of short-term estrogen replacement on DRG trkA mRNA levels, indicate that the regulation of DRG beta-PPT mRNA levels by estrogen requires target-derived NGF., (Copyright 2001 Academic Press.)

A population of adult dorsal root ganglion (DRG) neurons bind NGF with high affinity and express the trkA gene. In these cells, NGF regulates gene expression and function. Recently, a number of laboratories reported the presence of estrogen receptors in DRG neurons and profound effects of estrogen on DRG gene expression. Our laboratory, for example, has reported a significant and coordinate decrease in DRG trkA and beta-preprotachykinin (beta-PPT) mRNA levels following 90 days of daily estrogen injections to ovariectomized (OVX) rats. These data suggest, as has been suggested for medial septal cholinergic neurons, that estrogen may collaborate with NGF in the regulation of DRG neuronal gene expression and function. The current study examined further this potential collaboration in the DRG by determining the effect of short-term estrogen replacement in OVX rats on DRG trkA mRNA levels following sciatic nerve transection and the resulting removal of a vital source of NGF for those cells. In OVX rats, about 40% of lumbar DRG neurons contained trkA mRNA. Short-term estrogen replacement had no effect on the percentage of neurons containing trkA mRNA, but increased the mean trkA mRNA level in uninjured DRGs of OVX rats by 23%. Axotomy in OVX rats reduced the mean trkA mRNA level by 55% but did not significantly decrease the percentage of neurons containing the mRNA. Estrogen replacement, 7 days after axotomy, partially and significantly restored the mean trkA mRNA level. It was 49% greater than that of the untreated axotomized DRGs. It did not, however, significantly increase the percentage of DRG neurons containing trkA in axotomized DRGs. These observations show that short-term estrogen has an opposite effect on DRG neuronal trkA mRNA levels as compared to that of long-term estrogen demonstrated in our previous study. Moreover, the current data show that estrogen regulates trkA mRNA levels in the absence of target-derived NGF. These data suggest that estrogen may collaborate with NGF in the maintenance of normal adult DRG gene expression and function. Furthermore, these data suggest that loss of estrogen, such as that associated with menopause, may contribute to a decline in DRG neuronal function and an exacerbation of ongoing neuropathic processes., (Copyright 1999 Academic Press.)

Estrogen status has profound effects on cutaneous sensitivity in adult female rats. The presence of alpha-estrogen receptor mRNA and protein in NGF-dependent, adult female rat dorsal root ganglion (DRG) neurons raises the possibility that estrogen modulates cutaneous sensation by acting directly on primary afferent neurons, perhaps by altering their sensitivity to NGF. The present study examined the effect of long-term (90 days) daily injections of an estrogen preparation, Premarin (Wyeth-Ayerst, Radnor, PA), to ovariectomized adult rats on lumbar DRG high-affinity NGF receptor, trkA, mRNA levels, and on beta-preprotachykinin (beta-PPT) mRNA levels, which have been shown to be regulated by NGF. Two doses were used in the experiments, the higher dose being 10 times that of the lower dose. Such injections had an effect opposite that reported for short-term, acute estrogen treatment on DRG trkA mRNA levels. The current data show that long-term daily estrogen treatment decreases trkA mRNA levels by 36%. After 90 days of estrogen treatment, no dose effect was evident. Moreover, as would be expected if beta-PPT gene expression is regulated by NGF through the trkA receptor, long-term estrogen treatment decreased DRG neuronal beta-PPT mRNA levels by about 30%. As with trkA, there was no dose effect evident after 90 days of estrogen treatment. These data suggest the possibility that estrogen modulates DRG neuropeptide gene expression and, perhaps, cutaneous sensitivity by regulating NGF receptor gene expression., (Copyright 1999 Academic Press.)

Dorsal root ganglion (DRG) sensory neurons are particularly vulnerable to diabetes mellitus. There is evidence that the disease decreases both circulating and retrogradely transported neurotrophic factors that are essential to the normal maintenance and function of these cells. A substantive loss of trophic support should cause DRG neurons to respond as though they were axotomized and, like an axotomy, cause significant changes in cytoskeletal gene expression within these cells. Such changes might contribute to the deficits in sensory neuronal function that characterize diabetic neuropathy. The current study used quantitative in situ hybridization to test the hypothesis that streptozotocin-induced diabetes, like an axotomy, increases class III beta-tubulin gene expression and decreases neurofilament 68-kDa gene expression in lumbar DRG neurons. In animals that had been diabetic for 8 weeks with mean blood glucose levels of 340 mg/dl, lumbar DRG class III beta-tubulin mRNA mean steady-state levels were twofold higher than those in age-matched nondiabetic controls. Moreover, in the same animals, diabetes decreased lumbar DRG 68-kDa neurofilament mRNA mean steady-state levels by more than half. These data show that diabetes causes changes in primary sensory neuronal cytoskeletal gene expression that mimic those caused by axotomy. Moreover, they support the idea that a loss of neurotrophic support contributes to the pathogenesis of diabetic neuropathy., (Copyright 1998 Academic Press.)

Recently, adult female dorsal root ganglion (DRG) neurons were shown to express the estrogen receptor gene and to bind estrogen. This gene expression and binding is hormone dependent. Moreover, in a subpopulation of DRG neurons, the estrogen receptor is colocalized with high-affinity (trkA) and low-affinity (p75NGFR) receptors for nerve growth factor (NGF). In this NGF-responsive subpopulation of DRG neurons, estrogen regulates expression of the NGF receptor genes and may increase the sensitivity of these cells to the neurotrophin. The present study tested the hypothesis that neurofilament gene expression, which is regulated by NGF in these cells, is dependent on hormone status. In this study, ovariectomized (OVX) rats received either long-term physiological estrogen (conjugated estrogens; Premarin, Wyeth-Ayerst) replacement (low dose) or 10 times physiological levels (high dose). Quantitative in situ hybridization with an RNA probe for the 68-kDa neurofilament mRNA revealed a significant dose-dependent effect of Premarin on DRG neurofilament gene expression. In OVX animals receiving low-dose Premarin replacement therapy the mean steady-state 68-kDa mRNA level was as high as 4 times that of untreated OVX rats. High-dose therapy increased the mean 68-kDa neurofilament steady-state mRNA level to as much as six-fold that observed in untreated OVX animals. The estrogen-dependent upregulation of neurofilament gene expression appeared to occur in all DRG neurons, rather than in a subpopulation of those cells. These data suggest an important role for estrogen in the maintenance and function of primary sensory neurons. Whether estrogen directly regulates neurofilament gene expression or indirectly regulates it by increasing DRG neuronal sensitivity to neurotrophins or other growth factors remains to be determined.