Real-world outcomes of unrestricted direct-acting antiviral treatment for hepatitis C in Australia: The South Australian statewide experience.

In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C virus (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. A total of 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, P = .03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, P = .03) and younger age (OR 0.98, 95% CI 0.97-0.99, P = .05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23, 95% CI 0.07-0.74, P = .01) and genotype 3 (OR 0.23, 95% CI 0.12-0.43, P ≤ .01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials; however, a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlight the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets.

Rapid on-site assessment of specimens by biomedical scientists improves the quality of head and neck fine needle aspiration cytology.

OBJECTIVE: Immediate rapid on-site assessment (ROSA) of fine needle aspiration cytology (FNAC) specimens by biomedical scientists (BMS), the UK equivalent of cytotechnologists, or by pathologists may improve specimen quality and cellular adequacy rates for lymph node, head and neck and thyroid FNAC. The aim of this study was to evaluate the effect of introducing ROSA by BMS in an outpatient clinic setting. METHODS: The adequacy rate and sensitivity of histological diagnosis for lymph node, thyroid and salivary gland FNAC samples were determined before and after the introduction of BMS ROSA. The additional financial costs and time required to perform this service were also estimated. RESULTS: Thirty-one patients underwent ultrasound (US)-guided FNAC with ROSA and 151 without. ROSA reduced the number of FNAC insufficient in quality for diagnosis from 43% to 19% (P = 0.0194). The estimated additional cost for pathology per patient for ROSA was between £52.05 and £70.74, equivalent to €65.40/US $83.90 and €88.89/US $114.0, respectively, an increase of between 28% and 49% from the original cost. ROSA necessitated an additional 6 minutes clinic time per patient, reducing the number of patients that could be seen in an average clinic from 13 to 10 as well as requiring increased laboratory time for FNAC slide assessment. CONCLUSION: ROSA by suitably trained biomedical scientists and with appropriate consultant pathologist support can improve the quality of FNAC sampling for head and neck lesions. Although ROSA resulted in both additional financial and time costs, these are more than likely to be offset by a reduction in patients returning to clinic for repeat FNAC or undergoing unnecessary surgery.

Transitions for older people with learning disabilities and behaviours that challenge others, and their family carers: a merged protocol for two rapid scoping reviews of evidence.

BACKGROUND: There are over 1 million adults with a learning disability in the UK, of whom approximately 20% displaying behaviours that challenge others. Two thirds of people with learning disabilities live in the family home. As they and their family carers age, both are likely to face particular difficulties and stresses, but there is little understanding of their experiences and needs. To address this evidence gap, our main objective is to undertake two rapid scoping reviews that will collectively focus on the health and social care needs, experiences, service interventions and resources of older people with learning disabilities and behaviours that challenge others, and their family carers. Both reviews will focus on issues relating to forward planning and transitions to different care contexts. The study is part of a research project funded by the National Institute for Health Research No.129491. METHODS: We propose to address the need for evidence via two rapid scoping reviews. We will include published and unpublished (grey) literature, encompassing empirical research, policy and practice guidance and lay resources to support decision-making. We will search multiple electronic databases, hand search references lists, and use expert guidance to identify potential evidence. The following databases were used for research and grey literature: CINAHL; Healthcare Management Information Consortium (HMIC); NHS Evidence; Scopus; Turning Evidence Into Practice (TRIP); Web of Science (WoS); Google (first 5 pages); and Google Scholar (first 5 pages). For RR2, additional intended databases are the Carer Research Knowledge Exchange Network (CAREN) and Social Care Institute for Excellence (SCIE). Two reviewers will independently screen all citations and full-text articles for inclusion. One reviewer will extract data, with an independent review undertaken by the research team. Critical appraisal will depend on the nature of included evidence. Narrative synthesis will be collaboratively developed, with descriptive information presented in tables summarising study characteristics and thematic analysis of findings presented in the main text. Dissemination will be through journal publication, conference presentations and written short-form, easy-read versions of articles and audio-video clips for lay audiences. DISCUSSION: We will consider the strengths and limitations of our reviews, considering their impact on findings. We will summarise the main findings and provide an interpretation linked to the review questions and objectives. We will consider the implications of our findings for policy and practice, as well as future research addressing the support of older people with learning difficulties and behaviours that challenge others, and their family carers, in the context of transition to different care contexts in the UK. The protocol has been registered as Vseteckova, J., Jordan, J., Tilley, E., Larkin, M., Ryan, S., and Wallace, L. (2021, December 4). Transitions for older people with learning disabilities and behaviours that challenge others, and their family carers: a merged protocol for two rapid scoping reviews of evidence. Retrieved from osf.io/jzrn9.

A novel tool to evaluate bias in literature on use of biologic mesh in abdominal wall hernia repair.

PURPOSE: Biologic meshes are being increasingly used for abdominal hernia repair in high-risk patients or patients with a previous history of wound infection, due to their infection-resistant properties. Several studies have been carried out to assess whether biologic mesh is superior to synthetic mesh, as well as to establish guidelines for their use. Unfortunately, most of these studies were not rigorously designed and were vulnerable to different types of bias. The systematic reviews that have been published so far on this topic contain the same biases and limitations of the primary articles that are analyzed. The lack of a literature review on the bias on the use of biological mesh prompted us to conduct the literature search, assessment and plan this article. METHODS: We performed a literature search in PubMed, Embase and Cochrane databases of systematic reviews on biologic mesh for ventral hernia repair. The literature review was conducted using the Population, Intervention, Comparisons, Outcomes and Design approach. We identified 40 studies that matched the stringent criteria we had set. We then created a 13-point instrument to assess for bias and applied it on the primary studies that we intended to analyze. RESULTS: Most primary studies are case series or case reports of patients undergoing abdominal hernia repair with biologic mesh, without any comparison group, and the inclusion of cases was only specified to be consecutive in 6 out of 40 cases. In terms of assessing outcomes, in none of the 40 articles were the outcome assessors blinded to the intervention or exposure status of participants. CONCLUSION: The instrument that we created could allow to assess the risk of bias in different kind of studies. Our assessment of the studies based on the criteria that we had set up in the instrument clearly identified that further research needs to be done due to the lack of unbiased studies regarding the use of biologic meshes for abdominal hernia repair.

Recovery of struvite from stored human urine.

In previous work, synthetic urine was used as a readily available proxy for real urine for determining the factors which affect the recovery of struvite from urine. Based on these findings with synthetic urine, we recovered struvite from real urine and, thus, showed that a) the synthetic urine served as an adequate model for determining the processes which affect struvite precipitation, and b) high quality struvite can be recovered from real human urine. For urine solutions diluted up to four times, an average of 23% of phosphorus and 80% of magnesium was precipitated naturally; the remaining supernatant was then dosed with magnesium to recover the phosphorus still in solution. The struvite recovered was approximately 99% pure regardless of storage conditions although full strength urine was best for struvite recovery since it contains the greatest mass of harvestable phosphorus. We conclude that synthetic urine can be used as a proxy for real urine when investigating struvite recovery provided the synthetic mixture is consistent with the expected composition in the specific context.

Effects of storage on phosphorus recovery from urine.

In laboratory experiments using synthetic urine the effect of temperature, faecal contamination, dilution and headspace on urine to be used as a feedstock for struvite recovery were examined. The effects of adding different quantities of magnesium on the amount of phosphorus that could be removed from solution was also examined. An average of 62% of phosphorus could be removed in the form of struvite when magnesium was added to the urine solution after ureolysis had forced the precipitation of calcium and magnesium minerals. Dilution and the presence of faecal urease were found to affect the rate of ureolysis but not the purity of the struvite recovered. These results indicate that, by simply storing urine until it achieves a pH of 8 or greater, struvite can be recovered from source-separated urine with only a magnesium addition.

Occult stenosis of the common carotid artery complicating mandibular reconstruction with a fibular free flap.

An unsuspected severely stenosed common carotid artery that compromised a free flap for mandibular reconstruction is described. To our knowledge no one has advocated the assessment of the carotid tree before transfer of free tissue. We suggest that patients with several risk factors for peripheral vascular disease should have colour flow duplex imaging of the carotid system if transfer of free tissue is being considered.

Relative HLA-DRB1*13 allele frequencies and DRB3 associations of unrelated individuals from five US populations.

The frequencies of 30 HLA-DRB1*13 alleles and 15 DRB3 alleles were determined for the 5 major U.S. ethnic populations: Caucasians, African Americans, Asian/Pacific Islanders, Hispanics, and Native Americans. A random sampling (163) of DRB1*13-positive individuals from each self-described ethnic group was selected out of a pool of 82,979 unrelated individuals, providing at least an 80% probability of detecting a rare allele that occurred at 1%. These 815 samples were subjected to allele-level SSOP typing and/or DNA sequencing which identified 11 different DRB1*13 alleles. DRB1*1301 and DRB1*1302 were the most common alleles seen in the five major ethnic groups while DRB1*1304 was not detected among Caucasians and DRB1*1305 was not detected among African Americans. DRB1*13 allele diversity was surprisingly more limited among African Americans compared to both Caucasians and Asian/Pacific Islanders. To determine the extent of DRB1*13-DRB3 associations, 504 of these samples expressing only one DRB3-associated DRB1 allele were subjected to PCR-SSOP typing and 14 DRB1*13-DRB3 haplotypes were detected. The distribution revealed that African Americans were significantly different from Caucasians, Asian/Pacific Islanders, and Hispanics. Allele frequency studies such as this further support previous findings that the distribution of HLA types can differ significantly among different ethnic populations.

Low-cost struvite production using source-separated urine in Nepal.

This research investigated the possibility of transferring phosphorus from human urine into a concentrated form that can be used as fertilizer in agriculture. The community of Siddhipur in Nepal was chosen as a research site, because there is a strong presence and acceptance of the urine-diverting dry toilets needed to collect urine separately at the source. Furthermore, because the mainly agricultural country is landlocked and depends on expensive, imported fertilizers, the need for nutrient security is high. We found that struvite (MgNH(4)PO(4)·6H(2)O) precipitation from urine is an efficient and simple approach to produce a granulated phosphorus fertilizer. Bittern, a waste stream from salt production, is a practical magnesium source for struvite production, but it has to be imported from India. Calculations show that magnesium oxide produced from locally available magnesite would be a cheaper magnesium source. A reactor with an external filtration system was capable of removing over 90% of phosphorus with a low magnesium dosage (1.1 mol Mg mol P), with coarse nylon filters (pore width up to 160±50 µm) and with only one hour total treatment time. A second reactor setup based on sedimentation only achieved 50% phosphate removal, even when flocculants were added. Given the current fertilizer prices, high volumes of urine must be processed, if struvite recovery should be financially sustainable. Therefore, it is important to optimize the process. Our calculations showed that collecting the struvite and calcium phosphate precipitated spontaneously due to urea hydrolysis could increase the overall phosphate recovery by at least 40%. The magnesium dosage can be optimized by estimating the phosphate concentration by measuring electrical conductivity. An important source of additional revenue could be the effluent of the struvite reactor. Further research should be aimed at finding methods and technologies to recover the nutrients from the effluent.

Cranial blind-ending branch of a bifid ureter. Report of 3 cases.

Three cases of cranial blind-ending branches of bifid ureters are presented, all occurring in women. None was associated with complications requiring surgery, suggesting that they were of little clinical significance in these patients. The anomaly was best shown with oblique views at intravenous urography.

CT demonstration of pituitary stalk relapse in childhood acute lymphoblastic leukaemia.

Central nervous system relapse in childhood acute lymphoblastic leukaemia (ALL) occurs in 8% (all risks). Leptomeningeal infiltration is the usual form of relapse and pituitary stalk involvement is rarely found. We report the CT demonstration of pituitary stalk relapse with endocrine evidence of disruption of the hypothalamo-pituitary axis.