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Virological failure occurs in a small proportion of people treated for hepatitis C virus (HCV) with direct-acting antiviral (DAA) therapies. This study assessed retreatment for virological failure in a large real-world cohort. REACH-C is an Australian observational study (n=10843) evaluating treatment outcomes of sequential DAA initiations across 33 health services between March 2016 to June 2019. Virological failure retreatment data were collected until October 2020. Of 408 people with virological failure (81% male; median age 53; 38% cirrhosis; 56% genotype 3), 213 (54%) were retreated once; 15 were retreated twice. A range of genotype specific and pangenotypic DAAs were used to retreat virological failure in primary (n=56) and tertiary (n=157) settings. Following sofosbuvir/velpatasvir/voxilaprevir availability in 2019, the proportion retreated in primary care increased from 21% to 40% and median time to retreatment initiation declined from 294 to 152 days. Per-protocol (PP) sustained virological response (SVR12) was similar for people retreated in primary and tertiary settings (80% vs 81%; p=1.000). In regression analysis, sofosbuvir/velpatasvir/voxilaprevir (vs. other regimens) significantly decreased likelihood of second virological failure (PP SVR12 88% vs. 77%; adjusted odds ratio [AOR] 0.29; 95%CI 0.11-0.81); cirrhosis increased likelihood (PP SVR12 69% vs. 91%; AOR 4.26; 95%CI 1.64-11.09). Indigenous Australians had lower likelihood of retreatment initiation (AOR 0.36; 95%CI 0.15-0.81). Treatment setting and prescriber type were not associated with retreatment initiation or outcome. Virological failure can be effectively retreated in primary care. Expanded access to simplified retreatment regimens through decentralised models may increase retreatment uptake and reduce HCV-related mortality.

BACKGROUND: The COVID19 pandemic highlights the need for contingency planning in the event of blood shortages. To increase platelet supply, we assessed the operational impact and effect on platelet quality of splitting units prior to storage. STUDY DESIGN AND METHODS: Using production figures, we modeled the impact on unit numbers, platelet counts, and volumes of splitting only apheresis double donations into three units (yielding ⅔ doses), or all standard dose units in half. To assess quality, eight pools of three ABO/Rh-matched apheresis (Trima Accel) double donations in plasma were split to ⅔ and ½ volumes in both Terumo and Fresenius storage bags. These were irradiated and subject to maximal permitted periods of nonagitation (3 × 8 h) before comparing platelet quality markers (including pH, CD62P expression) to Day 9 of storage. RESULTS: Splitting all double donations into three predicted inventory expansion of 23% overall whereas halving all standard dose units clearly doubles stock. In our study, ⅔ and ½ doses contained 153 ± 15 × 109 (~138 ml) and 113 ± 11 × 109 (~102 ml) platelets respectively. Following storage, higher pH was observed in ⅔ than in ½ doses and in Terumo compared to Fresenius bags. The higher pH was reflected in better quality markers, including lower CD62P expression. Despite the differences, on Day 8 (of pH monitoring at expiry) all ⅔ doses and most ½ doses were ≥pH 6.4. CONCLUSION: A strategy to split apheresis platelets in plasma to lower doses is feasible, maintains acceptable platelet quality, and should be considered by blood services in response to extreme shortages.

Background In adults ageing is accompanied by changes in limb volume and skin biomechanical properties. Objectives To explore the relationship between body size, aging, skin biomechanics, and leg volume, VLeg and to define predictive equations linking leg volume with these properties. Methods Sixty-two healthy adults (Age 18-80 years, M:F 45:55) were recruited. Anthropomorphic measures were recorded along with VLeg (via circumferential method) and skin tone, stiffness, and elastance (via tonometry). Regression analysis was performed to define relationship between the measured parameters. Results In healthy adults bilateral VLeg were the same regardless of leg or sex, 5791 ± 1363 for females and 6151 ± 1203 mls for males. VLeg was positively correlated to body weight, where VLeg (mls) = 1058 + 69 × Wt (kg) for females and VLeg (mls) = 539 + 65 × Wt (Kg) of body weight for males. Skin surface biomechanical properties varied with sex, leg volume, and location on the leg with the malleolus exhibiting the stiffest surface. Conclusion The study shows that anthropometric measures change with sex and leg size are multifactorial and body weight, sex, and skin condition as important determinant factors of leg volume.

In a larger study where the aim was to investigate choice and control in decision making, the role of partners was significant. Reported here are the experiences of those partners of young people with cancer.A qualitative, exploratory case study approach was used.In the larger study, 22 participants were recruited including five adolescents and young adults with cancer, two sets of parents/carers and three individual parents, five healthcare professionals linked to the adolescent or young adult with cancer and five friends or partners. Data were collected between February 2014 and February 2015 and included interviews, non-participant observation and documentary analysis.Three themes were identified relating to partner experience derived from partner and patient interview data: "practical support", "putting your partner first" and "acting as a confidante/ally".These findings reveal new knowledge of partner experience when adolescents and young adults have cancer. Richer in-depth understandings of partner experience are required to improve the care of adolescents and young adults with cancer and those around them.These findings will inform the development of guidance and further research which will enhance the knowledge of partner experience for those involved in cancer care in the adolescent and young adult age group.目的: 研究的主要目的是研究决策中的选择和控制,服务者在决策中起很大作用。研究主要内容是患癌青年服务者的经历。 设计: 研究使用定性,案例探索研究方法。 方法: 研究参与者共有22位,包括5位患癌青少年和青年、两对父母/照顾者和3 位离异父母、5位患癌青少年和青年分别的健康护理专家和5位朋友。数据收集始于2014年2月到2015年2月截止,收集数据包括采访、局外观察、纪录片分析。 结果: 从服务者和病人采访数据中得出三类主题的服务患癌青少年和青年经历:“实际服务”“以服务者为第一位”“作为知己或盟友” 结论: 研究发现服务患癌青少年和青年的新经历。要提高对患癌青少年和青年的服务,首先需要对这些服务患癌青少年和青年的经历有深刻的丰富的理解。 影响: 这一发现将会促进指导政策的发展和更深入的研究,进一步促进人们对服务患癌青少年和青年经历的理解。.

To explore the experiences and needs of partners who are supporting adolescents and young adults with cancer. The diagnosis of cancer at any age is significant. Uniquely, in adolescents and young adults this is set against the backdrop of early adult development. This is at a time when young people may be embarking on new experiences and the development of romantic relationships is no exception. There is limited evidence of how partners cope during this time and what their role is alongside how the relationship may change over time.An exploratory qualitative study using narrative enquiry.The protocol was approved in February 2018 and data will be collected between May - December 2018. The theoretical approach will incorporate positioning theory by considering the contextual situation of the partner with reference to their stories, including their rights and duties. Two interviews will be undertaken which will be approximately 2 months apart, where participants will be asked to share their stories. They will also be given a diary at the end of the first interview to record their thoughts about their role and relationship. The diary and interview data will be thematically analysed.It is envisaged that the study will culminate in the identification of key themes which will illuminate the experiences, needs and roles of partners of adolescents and young adults with cancer.These findings will inform the development of guidance which will help partners in the future in this area of practice.目的: 探讨支持青少年和青年癌症患者伙伴的经验和需求。任何年龄的癌症诊断都很重要。不同的一点是,在青少年和青年成年人中,这是在成人早期发育的背景下进行的。这段时间,年轻人可能会开始新的经历,恋爱关系的发展也不例外。只有有限的证据表明,伴侣在这段时间是如何应对的,他们的角色是什么,以及随着时间的推移,关系可能会发生什么变化。 设计: 一项探索性质的研究,使用叙述研究法。 方法: 该议定书于2018年2月获得批准,将于2018年5月至12月期间收集数据。该理论方法将结合定位理论,考虑合作伙伴的背景情况,结合他们的故事,包括他们的权利和义务。将进行两次访谈,时间大约相隔2个月,要求参与者分享他们的故事。在第一次面试结束时,他们还会得到一个日记本,记录下他们对自己角色和关系的想法。日记和采访数据将按主题分析。 讨论: 预计这项研究将最终确定关键主题,阐明青少年和青年癌症患者的经验、需要和伙伴的作用。 影响: 这些调查结果将有助于制定指导方针,以便今后在这一实践领域帮助伙伴。.

Industry studies and public policy (IS&PP) is a research domain that seeks to further our understanding of industrial practices and managerial challenges by explicitly considering contextual details in the design and interpretation of studies. These details can also be vital considerations when shaping public policies. This article reviews a sample of IS&PP publications and analyzes the content of 180 selected papers - 85 papers published in the Production and Operations Management (POM) journal and 95 research papers published in related journals between 1992 and 2014. Analysis of the sampled data set and examination of exemplar papers provide four findings. First, studies in different industries emphasize different themes of operational decisions. This difference in emphasis reveals potential research opportunities, especially for conducting inter-industry studies. Second, our analysis reveals a shift in focus. Earlier studies contain a mix of benchmarks and inter-industry comparisons, while the later studies tend to focus on context specific, single-industry studies. This trend highlights the potential for developing new measures and multi-method approaches. Third, we report on empirics-analytics-empirics cycles that reveal gaps for building novel theories. Finally, we observe that the relationship between POM decisions and public policy is bi-directional. This highlights the need to jointly examine operational decisions with policy considerations, especially in information goods, healthcare, sustainable operations and high-tech manufacturing industries.

Aim A discussion which aims to explore the diversity of decision-making during teenage and young adult cancer treatment. The discussion will be related to the concepts of autonomy, dependence and decision-making in this age group. Background The experience of cancer involves a significant series of treatment decisions. However, other non-treatment decisions also have to be made which can relate to any aspect of everyday life. These decisions occur against the backdrop of young people's disease experience. Design Discussion paper. Data sources A literature search for the period 1990–2013 was undertaken. This included searching the following databases: Cumulative Index for Nursing and Allied Health Literature (CINAHL), SCOPUS, Medline, DARE, Applied Social Sciences Index and Abstracts (ASSIA), (Psych Info) and The Cochrane Library. Implications for nursing There is a lack of evidence into the experience of everyday decisions made by young people during cancer treatment. This may affect them in the form of unmet needs that nurses, or other professionals, fail to appreciate. Conclusion Further exploration of how teenagers and young adults experience the range and process of decision-making during cancer treatment could be useful in helping to provide effective supportive care for this age group.

Indigenous Australians experience a significant health burden from chronic hepatitis B infection; however, the strain of hepatitis B virus (HBV) found among Indigenous Australians has not been well characterized. Blood samples were collected from 65 Indigenous Australians with chronic HBV infection from across the Top End of Australia's Northern Territory. Phylogenetic analysis of HBV from these samples revealed that 100% of the isolates were genotype C, sub-genotype C4, expressing the serotype ayw3. This strain is a divergent group within the HBV/C genotype, and has only been described in Indigenous Australians. Evidence of recombination was suggested by discordant phylogenetic clustering of the C4 sequences when comparing the full genome to the surface region and confirmed by recombination analysis which showed the surface gene region to be most closely related to genotype J, while the remaining regions of the genome were most similar to genotype C sequences. Mutational analysis revealed the presence of multiple mutations that have been linked with more rapid liver disease progression and an increased risk of hepatocellular carcinoma. These mutations were detected in the majority of sequences examined. Variants associated with vaccine failure were detected as the predominant viral quasi-species in 3/35 samples. In summary, the HBV C4 variant found in this population has a high potential to cause advanced liver disease and to escape vaccination programs. Further in vitro functional and natural history studies are warranted in order to determine the clinical and public health consequences of infection with the HBV C4 variant in these communities.

Supply chain integration is increasingly seen as a method to obtain flexibility and, consequently, to provide competitive advantage for firms within a supply chain. Product modularity, either in concert with or independent of such integration, can also produce flexibility for firms within a supply chain. In this proof-of-concept research, we explore whether the supply chain network affects each constituent firm's market valuation and how decisions regarding the level of supply chain integration and the usage of product modularity are associated with the value of the supply chain. We develop a method to identify and measure the supply chain's effect on each constituent firm's market valuation. Results indicate that greater integration is associated with a higher supply chain valuation, whereas increasing aggregated product modularity across the supply chain relates to a lower supply chain value. However, when combined, the interaction of aggregated product modularity and supply chain integration is positively associated with the supply chain's valuation.

Background and Aim The hepatitis B surface antigen was first described in the blood of an Indigenous Australian man, yet little is known about its molecular epidemiology in this population, in which it is endemic. The study aimed to determine the clinical and molecular epidemiology of hepatitis B virus (HBV) in Indigenous people from northern Australia. Methods Following ethics approval and informed consent, blood specimens and clinical details from Indigenous adults known to be infected with HBV and who were born and raised in Indigenous communities in northern Australia were obtained. HBV genotypes were determined in isolates with sufficient HBV DNA by polymerase chain reaction by sequencing of the polymerase/surface gene. Results Between June 2010 and June 2012, 65 patients were recruited from six different regions of northern Australia. Thirty-two patients (49%) were hepatitis B e-antigen-positive, and 48% were hepatitis B e-antibody-positive. No patients were found to be coinfected with hepatitis C virus or human immunodeficiency virus. Of the 49 samples with sufficient viral load for genotyping, 100% were infected with genotype C4, previously only reported from two Indigenous Australians. All isolates had wild-type polymerase gene sequences despite 14 currently or previously receiving antiviral treatment. The canonical sG145R vaccine-escape variant was detected in the surface antigen of virus from two patients. Conclusions The exclusive HBV genotype in this ancient population is genotype C4. Whole genome sequencing and clinical follow-up of this cohort are in progress, with the aim of exploring the clinical significance of these findings.

Aim: To describe the incidence and prevalence of blood-borne viruses (BBV) including: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) and human T-cell leukaemia virus type-1 (HTLV) in the haemodialysis-dependent population of the Top End of the Northern Territory (TENT). Methods: We retrospectively reviewed the serology of BBV in a longitudinal fashion in the haemodialysis-dependent population treated in the TENT of Australia from 2000 to 2009 inclusive. HBV, HCV, HIV and HTLV serology on commencement of dialysis and at exit or January 2010, whichever was earlier, as well as demographic details were collected. Patients with a change in serological status had all serology reviewed. Results: Four-hundred and forty patients were included in the analysis. Of these, 84.3% were Indigenous and 55.4% female, with a median age of 50 (IQR 43–59) years at the commencement of haemodialysis. Evidence of past HBV infection was documented in 42.7% and 8.9% were hepatitis B surface antigen-positive. Positive serology for HTLV was documented in 2.2%, 1.6% were hepatitis C antibody-positive and no individual was HIV-positive. Three patients had a definite change in their HBV serology over time; this equates to an absolute seroconversion risk of 0.1 per 100 person years or 0.0006 per dialysis episode. Conclusions: In this cohort, there was a high rate of past and current hepatitis B infection but low rates of seroconversion while on haemodialysis.

Aim. This article reports a randomised controlled trial to determine the efficacy of antenatal pelvic floor muscle exercises in the primary prevention of postpartum stress incontinence in primiparous women. Background. Pelvic floor muscle exercises are effective in treating stress incontinence, yet prevention studies demonstrate equivocal findings. Design. Randomised controlled trial. Method. Pregnant women recruited from two hospitals in North-west England were randomised to an intervention (n = 141) or control group (n = 145). Data were collected from 2005–2006. The intervention comprised four sessions of taught pelvic floor muscle exercise training during pregnancy and 8–12 maximal contractions repeated twice daily at home. A modified Bristol Female Lower Urinary Tract Symptom questionnaire, Leicester Impact Scale and Three Day Diary were administered at 20 and 36 weeks of pregnancy and three months postpartum. Results. The intervention group was more likely to exercise their pelvic floor muscles compared to controls at 36 weeks (p = 0·019) and three months (0·022), reporting fewer episodes of incontinence and a lower score on the Leicester Impact Scale. However, these differences were not statistically significant. Conclusion. Significant differences were not demonstrated between the groups in relation to incontinence episodes and degree of bother of symptoms postpartum, although trends indicate a positive effect. Further research is necessary to address issues of adherence and the effect of pelvic floor muscle exercise undertaken during pregnancy on postpartum stress urinary incontinence. Relevance to clinical practice. A proportion of women did not meet the required attendance at antenatal class, furthermore, few exercised their pelvic floor muscles during pregnancy according to instructions. Health professionals need to find ways to instruct and motivate women to perform pelvic floor muscles exercises regularly during pregnancy and the postpartum.

Each United Kingdom regional postgraduate deanery offers courses and educational support for the NHS (National Health Service) primary care dental team, primarily through networks of tutors (dental educators). After reporting literature on effective continuing education and the role of evaluation, this article provides an analysis of five educational evaluations (2005–08), identifying key messages and distilling ways to enhance educational support for the UK dental team. These evaluations adopted case study design and principally employed interviews (n=51) and questionnaires (n=221). The studies’ key messages and recommendations are as follows: clarify dental educator roles; provide strategic management and educational support for educators; ensure continuing education is matched to the learning needs of dental teams and specific groups; and use practice (office) visits to support practice (team) development plans. Evaluation enables initiatives to be evidence-informed, focus effort where most needed, argue for continued funding, and give voice to stakeholders. However, there is added value in a collective consideration of evaluation findings from related studies. Doing this has identified ways to enhance the strategic development of educational support for the UK dental team and is applicable in a wider context both nationally and internationally.

In the authors' research with Pakistani and Bangladeshi heritage parents, some teachers, head teachers and other educational professionals referred to the South Asian parents as ‘hard to reach’. Whilst it was clear from the parents that they were not very, and in some cases not at all, involved in their children's schools and knew little about the education system or what their children were doing in school, it was also very apparent that the parents were not ‘difficult’, ‘obstructive’, or ‘indifferent’—the kind of behaviour ‘hard to reach’ implies. The article therefore considers that rather than parents being ‘hard to reach’, it is frequently the schools themselves that inhibit accessibility for certain parents. The authors challenge the cultural interference model, arguing that it is incorrect and pathologises parents. The article arises out of a two‐year, Economic and Social Research Council funded, qualitative study of Bangladeshi and Pakistani heritage families and schools, in the north‐east of England.

During the 1990s, there was considerable emphasis on promoting particular kinds of pupil grouping as a means of raising educational standards. This survey of 2000 primary schools explored the extent to which schools had changed their grouping practices in response to this, the nature of the changes made and the reasons for those changes. Forty-eight per cent of responding schools reported that they had made no change. Twenty-two per cent reported changes because of the literacy hour, two per cent because of the numeracy hour, seven per cent because of a combination of these and twenty-one per cent for other reasons. Important influences on decisions about the types of grouping adopted were related to pupil learning and differentiation, teaching, the implementation of the National Literacy Strategy, practical issues and school self-evaluation.

Biting densities of the Simulium damnosum Theobald complex of blackflies and their levels of parasitism by Onchocerca volvulus (Leuckart) were compared at two ecologically contrasted sites in the Southern Province of Sierre Leone, West Africa: by the Tabe riverside close to Gbaiima village where onchocerciasis is hyperendemic (63.1% positive skin-snips) and in open rice fields 2 km from the mesoendemic (54.9%) village of Senehun. Using a combination of morphometric and enzyme electrophoresis techniques, the primary vector was found to belong to the S.sanctipauli subcomplex and was most probably S.soubrense 'B' (sensu Post, 1986). In the wet season biting activity took place throughout the day at the village, but had morning and evening peaks in the rice fields. Transmission of O.volvulus was detected at the village in all months except February-April, while in the rice fields it was detected only during September-November and May at one tenth the level of the village. There was a significant difference between the two sites in the proportion of parous flies carrying third stage larvae in the head, but not of other larval stages.