Biomarkers of liver fibrosis

Currently the only accepted method (gold standard) for the diagnosis of the fibrotic stages of chronic liver disease (CLD) is liver biopsy, to allow histological assessment. Liver biopsy is an invasive investigation associated with a range adverse events (e.g. pain, haemorrhage) limiting its serial usage in clinical practice. Additionally, its use is further reduced by sampling error and because histology is in effect a surrogate for clinical outcomes. Over recent years, alternative non-invasive biomarkers for the diagnosis of liver fibrosis have been developed. Initially developed in chronic viral hepatitis these have since seen their use expanded to include all aetiologies of CLD. Such markers can be divided into indirect ‘simple’ markers (e.g. transaminases, gamma-glutamyl transferase, platelet count), direct ‘complex’ markers (e.g. procollagen peptides I/III, Type IV collagen), cytokines (e.g. interleukin-10, transforming growth factor alpha) and imaging. Here, we discuss the clinical utility, limitations and development of non-invasive biomarkers in their use as diagnostic and prognostic tests

Could stool collection devices help increase uptake to bowel cancer screening programmes?

Objective: We aimed to understand the usage and acceptability of a faecal collection device (FCD) amongst participants of the NHS Bowel Cancer Screening Programme in order to influence future uptake. Setting: Men and women completing faecal occult blood test (FOBt) retests as part of the routine Bowel Cancer Screening Programme in Eastern England. Methods: A FCD and questionnaire was sent to all potential retest participants during a 1 month period collecting information on prior stool collection methods and ease of use and usefulness of the enclosed FCD. Results: Of 1087 invitations to participate, 679 (62.5%) participants returned their questionnaire. Of these 429 (63.2%) trialled the FCD at least once. 163 (38.4%) found the device made collecting their sample easier than previously, with 189 (44.6%) finding it made collection more difficult and 72 (17.0%) feeling it made no difference. Similar numbers reported finding that the FCD made collecting the sample more pleasant (130, 31.5%), less pleasant (103, 25.0%) and no different (179, 43.4%) compared to previous collection without a FCD. Conclusion: Although a small proportion of participants found the FCD helpful a considerable majority did not or did not use it at all. Offering FCDs is unlikely to produce a substantial increase in bowel cancer screening uptake

Facilitators and barriers to asylum seeker and refugee oral health care access: a qualitative systematic review

Objectives Asylum seekers and refugees (ASRs) encounter barriers when accessing oral health care (OHC). A qualitative systematic review was conducted to understand the perceptions, attitudes, behaviours and experiences of ASRs regarding their OHC. Themes were extracted to identify the barriers and facilitators ASRs face when accessing OHC. Data sources PubMed, APA PsycInfo, Cochrane Database, Web of Science and CINAHL were searched on 4 and 5 October 2022. Data selection Primary studies including ASRs of any age or nationality were included. Qualitative data of ASRs' lived experiences of oral health (OH) and accessing OHC were extracted. The Critical Appraisal Skills Programme quality appraisal tool was applied. Data synthesis Data findings were extracted and meta-aggregation performed using inductive reasoning. A total of 13 primary qualitative studies were included. Three barriers were identified, including difficulty accessing treatments and appointments, cultural and language changes, and ASRs' lack of OHC knowledge or incongruous beliefs surrounding OH. Two facilitators were identified as good OH education and support from care providers or government. Conclusions Decision-makers should adapt policy to facilitate access to OHC and educate ASRs on OH. More research is needed to understand the barriers and facilitators to OHC for other people groups who experience health inequalities

Completeness of primary intracranial tumour recording in the Scottish Cancer Registry 2011-12

IntroductionA high level of case ascertainment by cancer registries is essential to allow estimation of accurate incidence rates and survival. Nearly 20 years ago, researchers assessed the completeness and accuracy of registration of primary intracranial tumours (Scottish Cancer Registry [SCR]) compared to a database assembled in the context of a detailed incidence study carried out in the Lothian region of Scotland covering the period of diagnosis, 1989–1990.1 and 2 Disappointingly, SCR identified only 54% of cases, although the registry at that time did not attempt to collect information on ‘benign’ intracranial neoplasms which were included in the detailed incidence study. Even so, only 84% of neuro-epithelial tumours were identified by SCR, probably related in part to the fact that the cancer registry was not receiving neuropathology data from the regional neuro-oncology centre. An English study reported similar findings with only 52% of cases appearing in the regional cancer registry.3Over time, access to diagnostic techniques has improved alongside improvements and changes in classification and clinical coding. Furthermore, SCR now receives neuropathology data from all neuro-oncology centres in Scotland, and has sought to collect information on benign tumours of the brain and spinal cord since the year of diagnosis, 2000. In light of these developments, we aimed to determine the completeness of ascertainment of primary intracranial tumours by SCR through independent/clinical case ascertainment in NHS Lothian for the period of diagnosis, 2011–2012.MethodsScottish Cancer RegistrySCR operates by bringing together predominantly electronic information from hospital patient administration systems including patient discharges from hospital (Scottish Morbidity Record 01), radiotherapy, oncology, and pathology records; death records from National Records Scotland; and private hospital records.4 All primary malignant and benign brain tumours are recorded on the SCR.Inclusion and exclusion criteriaThis retrospective cohort study was restricted to the period of diagnosis between 1 January 2011 and 31 December 2012 and limited to adults (age ≥18 years on the date of diagnosis) with a postcode within the NHS Lothian health board region (mid-year population ∼650,000). The date of diagnosis was taken as i) the date of the first abnormal imaging, or ii) the date of biopsy/resection. Patients in whom there was no neuro-radiology or histology were excluded, i.e. diagnosis of prolactinoma had to be supported by blood tests and imaging.All suspected and histologically proven primary intracranial tumours (benign and malignant) of the brain and cranial nerves were counted, including primary central nervous system lymphoma. Meningeal, pituitary region and pituitary gland tumours were also included. Cerebral metastases, tumours of the spinal cord and spinal nerves, and recurrent intracranial tumours of any type were excluded.Extraction from the SCRData were extracted for the study period for all records including the following anatomical site codes selected from the third edition of the International Classification of Diseases for Oncology (ICD-O-3): C70.0; C70.9; C71; C72.2; C72.3; C72.4; C72.5; C72.8; C72.9; C75.1; C75.2; and C75.3 (all behaviour codes).Clinical case ascertainmentThree clinical sources were trawled as follows: i) neuro-oncology multidisciplinary team meeting (MDTM) minutes; ii) an endocrinology database; and iii) neuropathology records (sources i and ii are independent of the SCR data collection system). The neuro-oncology MDTM aims to discuss all intracranial tumours identified via any means including both benign and malignant tumours. The endocrinology database records all patients attending the endocrine outpatient clinics in the NHS Lothian region and each is assigned a diagnosis by a Consultant Endocrinologist. Both sources i and ii for the period 1 January 2011 – 31 March 2013 were reviewed manually by JRM. The neuropathology records hold information on all tissue samples analysed in the pathology system for NHS Lothian hospitals and an electronic extract was obtained using Systematized Nomenclature of Medicine codes matching those above. To ensure cases were true incident cases meeting the full inclusion criteria, each was cross-referenced with the patient's electronic secondary care medical record.AnalysisClinically ascertained cases were reconciled against the SCR extract. We have previously quantified the extent of misclassification of incidence year in the Scottish Cancer Registration database.5 We did not regard misclassifications of incidence year as missed or ‘over-diagnosed’ cases as there is no reason to believe that such misclassification is other than random.Completeness was defined as the proportion of intracranial tumours included in the SCR out of all those identified as diagnosed in residents of NHS Lothian area during the study period. Confidence intervals (95%) for completeness were calculated using the exact method.Completeness was calculated for all intracranial tumours with secondary analysis of completeness by tumour morphology and tumour grade (see Supplementary File for coding definitions).ResultsThere were 320 records of primary intracranial tumours registered on the SCR for the period of interest and 264 clinical cases were ascertained. Fig. 1 shows the final ascertainment of clinical cases missing from the SCR

Does advice based on biomarkers of liver injury or non-invasive tests of liver fibrosis impact high-risk drinking behaviour: A systematic review with meta-analysis

Background: Alcohol dependence affects over 240 million people worldwide and attributed to 3 million deaths annually. Early identification and intervention are key to prevent harm. We aim to systematically review literature on the effectiveness of adding advice based on biomarkers of liver injury or non-invasive tests of liver fibrosis (intervention-based advice ) to prevent alcohol misuse. Methods: Electronic search was conducted on Ovid Medline, PubMed, EMBASE, Psychinfo and CINAHL for articles published up to end of February 2020. Additionally, we searched study citations, Scopus, Ethos and Clinical trials. The primary outcome measure was changed in self-reported alcohol consumption analysed by random-effects meta-analysis. Secondary outcomes included change to liver blood markers and alcohol-related health outcomes.Results: 14 RCT and 2 observational studies comprising n=3763 participants were included. Meta-analyses showed a greater reduction in alcohol consumption and liver biomarkers for the intervention compared to control group: mean difference for weekly alcohol intake was -74.4 gram/week (95%CI -126.1, -22.6, p=0.005); and mean difference for GGT -19.7 IU/L (95% CI -33.1, -6.4, p=0.004). There was a higher incidence of alcohol attributed mortality, number of days spent in the hospital, physician visits and sickness absence in the non-intervention group. The quality of the included studies was moderate for RCT’s and high for observational studies. Conclusions: The review confirmed a significant association between the addition of intervention-based advice in routine care to the reduction of harmful alcohol consumption, GGT and alcohol-related mortality. The findings support the inclusion of this type of advice in routine alcohol care

Trends in indirect liver function marker testing in Wales from 2000 to 2017 and their association with age and sex: an observational study

Objective If non-invasive markers of liver fibrosis were recorded frequently enough in clinical practice, it might be feasible to use them for opportunistic community screening for liver disease. We aimed to determine their current pattern of usage in the national primary care population in Wales.Design Using the Secure Anonymised Information Linkage (SAIL) Databank at Swansea University (2000–2017), we quantified the frequency of common liver blood tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count and albumin) used in fibrosis marker algorithms. We examined measurement variation by age and sex.Results During the 18-year study period, there were 2 145 178 adult patients with at least one blood test available for analysis. Over the study period, the percentage of SAIL patients receiving an ALT test in each year increased from 2% to 33%, with platelet count and albumin measurement increasing by a similar factor. AST testing, although initially rising, had decreased to 1% by the end of the study. AST and ALT values varied by age and sex, particularly in males with the upper normal range of ALT values decreasing rapidly from 90 U/L at age 30 to 45 U/L by age 80.Conclusion The reduction in AST testing to only 1% of the adult population limits the use of many non-invasive liver marker algorithms. To enable widespread screening, alternative algorithms for liver fibrosis that do not depend on AST should be developed. Liver fibrosis markers should be modified to include age-specific and sex-specific normal ranges

Enhanced detection services for developmental dysplasia of the hip in Scottish children 1997-2013

Background Developmental dysplasia of the hip (DDH) remains common. If detected early, DDH can usually be corrected with conservative management. Late presentations often require surgery, and have worse outcomes. Objective We estimated the risk of undergoing surgery for DDH by age 3 years before and after the introduction of enhanced DDH detection services. Design Retrospective cohort study Setting Scotland, 1997/98 – 2010/11 Patients All children Methods Using routinely collected national hospital discharge records we examined rates of first surgery for DDH by age 3 by March 2014. Using a difference in difference analysis we compared rates in two areas of Scotland before (to April 2002) and after (from April 2005) implementation of enhanced DDH detection services to those seen in the rest of Scotland. Results For children born in the study period, the risk of first surgery for DDH by age 3 was 1.18 (95%CI 1.11-1.26) per 1,000 live births (918/777,375). Prior to April 2002, the risk of surgery was 1.13 (95%CI 0.88-1.42) and 1.31 (95%CI 1.16-1.46) per 1,000 live births in the intervention and non-intervention areas respectively. In the intervention areas, from April 2005, this risk halved (RR 0.47; 95%CI 0.32-0.68). The risk remained unchanged in other areas (RR 1.01; 0.86-1.18). The ratio for the difference in change of risk was 0.46 (95%CI 0.31-0.70). Conclusions The implementation of enhanced DDH detection services can produce substantial reductions the number of children having surgical correction for DDH