Hepatitis C treatment for difficult to access populations: can telementoring (as distinct from telemedicine) help?

BACKGROUND: Although hepatitis C virus (HCV) infection is curable, treatment of difficult to access populations (DTAP) presents unique challenges. Project ECHO (PE) (Extension for Community Healthcare Outcomes) is a telementoring programme adopted to support clinicians treating DTAP. AIMS: To determine if the PE model supports primary care clinicians treating HCV and to compare cohort of PE patients with those in a tertiary liver clinic (TLC). METHODS: Weekly PE group video conferences were conducted. Clinical information, laboratory indices, psychosocial elements and treatment outcomes, including sustained virological response (SVR) data were recorded in the first 100 consecutive cases and retrospectively compared to 100 consecutive patients seen at a TLC from July 2016 to April 2017. RESULTS: Some patient characteristics were similar between PE and TLC: gender (72% vs 75% male; P = 0.23), median age (45 vs 50; P = 0.344) and the proportion of treatment naïve patients (95.0% vs 90.9%). Treatment for HCV was commenced in 78% of the PE patients and 81% of the TLC patients; 67/68 of the TLC patients and 60/61 PE patients with virological follow up who completed treatment and attended follow up have confirmed SVR. PE patients are more likely to have ongoing substance use (44% vs 17% P < 0.001), be active intravenous drug users (32% vs 17%; P < 0.001) and polysubstance abusers (26% vs 7%; P < 0.001) and were more likely to be taking opioid substitution therapy (74% vs 20%; P < 0.001). Indigenous patients were three times more greatly represented in PE (15% vs 5%; P = 0.018). CONCLUSION: PE is an effective model to support primary healthcare providers treating HCV in DTAP with similar rates of treatment uptake and SVR compared to patients in TLC.

Public Health Unit notifications of hepatitis C and their follow-up in South Western Sydney, Australia.

OBJECTIVE: To determine hepatitis C virus (HCV) treatment rates among those newly diagnosed with the virus in the South Western Sydney Local Health District (SWSLHD) in NSW, Australia. STUDY TYPE: Cross-sectional study of patients newly diagnosed with HCV in SWSLHD, based on local Public Health Unit notification data from the second half of 2017. METHODS: A total of 200 consecutive notifications were enrolled in the study. Either the ordering clinician was interviewed, and/or data linkage with local hospital records performed, to determine rates of antiviral treatment in this cohort. Outcomes measured included the proportion of patients: started on antiviral treatment; referred to specialists for consideration of treatment; HCV ribonucleic acid (RNA) negative; and lost to follow-up. Descriptive analysis of factors contributing to those lost to follow-up was performed where available. RESULTS: The follow-up outcome of 93% of patients was traced. General Practitioners (GPs) diagnosed a similar number (102) of new HCV cases to those diagnosed by specialists (94). After detecting a patient as HCV antibody positive and confirming active infection, GPs preferred to refer patients to specialists (53%), rather than further evaluate and treat patients themselves (5%). The remainder of cases from the GP-detected group were lost to follow-up (26%), or HCV RNA negative (16%). Among the speciliast-detected patients, 41% were treated, 18% were lost to follow-up, 20% were RNA negative and the remainder were not treated for reasons including a concurrent diagnosis of hepatocellular carcinoma, or death. The most common reason patients were not started on antiviral treatment was loss to follow-up. CONCLUSION: We found that less than half (47%) of people in South Western Sydney newly diagnosed with HCV, in whom treatment was indicated, received antiviral medication in the 12 months following diagnosis.This figure excludes the 25% cases referred from general practice to specialists, in whom the treatment status is unknown. Approximately one in five newly diagnosed patients (22%) were lost to follow-up and 18% were RNA negative, indicating they had no active HCV infection.

Acceptability and preferences of point-of-care finger-stick whole-blood and venepuncture hepatitis C virus testing among people who inject drugs in Australia.

BACKGROUND: Uptake of hepatitis C virus (HCV) testing remains inadequate globally. Simplified point-of-care tests should enhance HCV diagnosis and elimination. We aimed to assess the acceptability of finger-stick and venepuncture HCV RNA testing among people who inject drugs (PWID). METHODS: Participants were enrolled in an observational cohort study with recruitment at 13 sites between June 2016 and February 2018. Capillary whole-blood collected by finger-stick and plasma collected by venepuncture were performed for Xpert® HCV viral load testing. Participants completed a questionnaire on acceptability of, and preferences for, blood collection methods. RESULTS: Among 565 participants (mean age, 44 years; 69% male), 64% reported injecting drugs in the last month, and 63% were receiving opioid substitution treatment. Eighty three percent reported that finger-stick testing was very acceptable. Overall, 65% of participants preferred finger-stick over venepuncture testing, with 61% of these preferring to receive results in 60 min. The most common reason for preferring finger-stick over venepuncture testing was it was quick (62%) followed by venous access difficulties (21%). The main reasons for preferring venepuncture over finger-stick testing were that it was quick (61%) and accurate (29%). Females were more likely to prefer finger-stick testing than males (adjusted OR 1.96; 95% CI 1.30, 2.99; p = 0.002). Among people with recent (previous month) injecting drug use, Aboriginal and/or Torres Strait Islander people were less likely than non-Aboriginal people to prefer finger-stick testing (adjusted OR 0.57; 95% CI 0.34, 0.9; p = 0.033). CONCLUSIONS: Finger-stick whole-blood collection is acceptable to people who inject drugs, with males and Aboriginal and/or Torres Strait Islander people with recent injecting drug use less likely to prefer finger-stick testing. Further research is needed to evaluate interventions integrating simplified point-of-care HCV testing to engage people in care in a single-visit, thereby facilitating HCV treatment scale-up.

The impacts of functional performance, behaviour and traffic exposure on road-crossing judgements of young children.

Using data from i) a simulated road-crossing task, ii) a battery of functional performance assessments, and iii) a survey of parents, some factors that may predict poor road-crossing skill were identified. Children aged between 6 and 10 years made road-crossing decisions in a simulated road environment in which time gap and speed of approaching vehicles were manipulated. Functional performance was examined using a range of tools designed to assess cognitive, perceptual, attentional and executive functioning. Parents also provided information on physical activity, exposure to traffic and road safety education. The results suggest that children predominantly made decisions based on distance gap and that younger children (6-7 year olds) were 12 times more likely than older children (8-10 year olds) to make critically incorrect (or unsafe) crossing decisions. Factors found to be associated with incorrect crossing decisions included lower perceptual, attentional, cognitive and executive performance, and independent travel. There were no gender differences associated with incorrect crossing decisions. This study has used a novel and safe way to identify 'at risk' groups of children and the findings have been used to develop and evaluate a practical educational and training program aimed at improving essential skills and strategies to cross roads safely amongst 'at risk' children.

The use of ultra-high pressure liquid chromatography with tandem mass spectrometric detection in the analysis of agrochemical residues and mycotoxins in food - challenges and applications.

In the field of food contaminant analysis, the most significant development of recent years has been the integration of ultra-high pressure liquid chromatography (UHPLC), coupled to tandem quadrupole mass spectrometry (MS/MS), into analytical applications. In this review, we describe the emergence of UHPLC through technological advances. The implications of this new chromatographic technology for MS detection are discussed, as well as some of the remaining challenges in exploiting it for chemical residue applications. Finally, a comprehensive overview of published applications of UHPLC-MS in food contaminant analysis is presented, with a particular focus on veterinary drug residues.

Maximum residue level validation of triclabendazole marker residues in bovine liver, muscle and milk matrices by ultra high pressure liquid chromatography tandem mass spectrometry.

Triclabendazole is the only anthelmintic drug, which is active against immature, mature and adult stages of fluke. The objective of this work was to develop an analytical method to quantify and confirm the presence of triclabendazole residues around the MRL. In this work, a new analytical method was developed, which extended dynamic range to 1-100 and 5-1000 µg kg(-1) for milk and tissue, respectively. This was achieved using a mobile phase containing trifluoroacetic acid (pK(a) of 0.3), which resulted in the formation of the protonated pseudomolecular ions, [M+H](+), of triclabendazole metabolites. Insufficient ionisation of common mobile phase additives due to low pK(a) values (<2) was identified as the cause of poor linearity. The new mobile phase conditions allowed the analysis of triclabendazole residues in liver, muscle and milk encompassing their EU maximum residue levels (MRL) (250, 225 and 10 µg kg(-1) respectively). Triclabendazole residues were extracted using a modified QuEChERS method and analysed by positive electrospray ionisation mass spectrometry with all analytes eluted by 2.23 min. The method was validated at the MRL according to Commission Decision (CD) 2002/657/EC criteria. The decision limit (CCα) of the method was in the range of 250.8-287.2, 2554.9-290.8 and 10.9-12.1 µg kg(-1) for liver, muscle and milk, respectively. The performance of the method was successfully verified for triclabendazole in muscle by participating in a proficiency study, the method was also applied to incurred liver, muscle and milk samples.

Investigation of the persistence of nitroxynil residues in milk from lactating dairy cows by ultra performance liquid chromatography tandem mass spectrometry.

Nitroxynil is an anthelmintic used in the treatment of liver fluke. In this study, six dairy cows were treated during lactation with Trodax, a 34% solution containing nitroxynil as its N-ethylglucamine salt, indicated for the treatment of fascioliasis in cattle and sheep. Samples were collected twice daily for 16 days and later at weekly intervals up to 58 days post-treatment. Nitroxynil residues were extracted from milk samples using acetonitrile; magnesium sulfate and sodium chloride were added to induce liquid-liquid partitioning and purified by dispersive solid phase extraction for clean-up. Nitroxynil was determined by ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in negative ionization mode. The limit of detection (CCα) of the method is 0.24 µg/kg. Maximum concentration of nitroxynil in the samples was in the range of 688-1358 µg/kg, with levels persisting for 58 days in four of the six lactating cows. Incurred nitroxynil samples were treated with sulfatase and ß-glucuronidase from Helix pomatia ; the results indicated the presence of glucuronide conjugates in samples at early withdrawal times. At later withdrawal times the concentration of free nitroxynil was lower than the concentration in the control samples, indicating potential degradation during enzymatic treatment.

Investigation of the persistence of levamisole and oxyclozanide in milk and fate in cheese.

In this study, dairy cows (n = six) were treated with an oral combination product containing levamisole (5 mg/kg body weight, (bw)) and oxyclozanide (10 mg/kg bw). Animals were milked twice daily up to day 16 post-treatment. Milk samples were subsequently analyzed by ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). The highest levels of levamisole (<600 µg/kg) and oxyclozanide (<25 µg/kg) were determined at first and third milking, respectively. Residues of levamisole and oxyclozanide were typically below reporting limits of 0.83 and 1 µg/kg respectively at the 11th and 13th milking, respectively. Soft (3 days ripening), hard (35 days ripening) and whey cheeses were produced from the milk samples collected from the first two milkings. Levamisole residues were found to concentrate in all cheese types. There was a 3-fold concentration effect for levamisole in mature cheese. Oxyclozanide residues were found to occur at lower levels in soft and hard cheese than milk with a 10-fold concentration in whey cheese compared to milk. The results of this study demonstrate that levamisole and oxyclozanide residues are rapidly excreted in dairy cows and milk is compliant after a few days. Oxyclozanide and levamisole residues were shown to be stable during the fermentation process and the whey heat treatment to persist in cheese.

A dual validation approach to detect anthelmintic residues in bovine liver over an extended concentration range.

This paper describes a method for the detection and quantification of 38 residues of the most widely used anthelmintics (including 26 veterinary drugs belonging to the benzimidazole, macrocyclic lactone and flukicide classes) in bovine liver using two different protocols for MRL and non-MRL levels. A dual validation approach was adopted to reliably quantify anthelmintic residues over an extended concentration range (1-3000 µg kg(-1)). Sample extraction and purification was carried out using a modified QuEChERS method. A concentration step was included when analysing in the low µg kg(-1) range. Rapid analysis was carried out by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS), which was capable of detecting residues to <2 µg kg(-1). The method has been single-laboratory validated according to the 2002/657/EC guidelines and met acceptability criteria in all but a few cases. The inclusion of 19 internal standards, including 14 isotopically labelled internal standards, improved accuracy, precision, decision limit (CCα) and detection capability (CCß).

Determination of anthelmintic drug residues in milk using ultra high performance liquid chromatography-tandem mass spectrometry with rapid polarity switching.

A new UHPLC-MS/MS (ultra high performance liquid chromatography coupled to tandem mass spectrometry) method was developed and validated to detect 38 anthelmintic drug residues, consisting of benzimidazoles, avermectins and flukicides. A modified QuEChERS-type extraction method was developed with an added concentration step to detect most of the analytes at <1 microg kg(-1) levels in milk. Anthelmintic residues were extracted into acetonitrile using magnesium sulphate and sodium chloride to induce liquid-liquid partitioning followed by dispersive solid phase extraction for cleanup. The extract was concentrated into dimethyl sulphoxide, which was used as a keeper to ensure analytes remain in solution. Using rapid polarity switching in electrospray ionisation, a single injection was capable of detecting both positively and negatively charged ions in a 13 min run time. The method was validated at two levels: the unapproved use level and at the maximum residue level (MRL) according to Commission Decision (CD) 2002/657/EC criteria. The decision limit (CCalpha) of the method was in the range of 0.14-1.9 and 11-123 microg kg(-1) for drugs validated at unapproved and MRL levels, respectively. The performance of the method was successfully verified for benzimidazoles and levamisole by participating in a proficiency study.

Benzimidazole carbamate residues in milk: Detection by Surface Plasmon Resonance-biosensor, using a modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) method for extraction.

A surface plasmon resonance (SPR) biosensor screening assay was developed and validated to detect 11 benzimidazole carbamate (BZT) veterinary drug residues in milk. The polyclonal antibody used was raised in sheep against a methyl 5(6)-[(carboxypentyl)-thio]-2-benzimidazole carbamate protein conjugate. A sample preparation procedure was developed using a modified QuEChERS method. BZT residues were extracted from milk using liquid extraction/partition with a dispersive solid phase extraction clean-up step. The assay was validated in accordance with the performance criteria described in 2002/657/EC. The limit of detection of the assay was calculated from the analysis of 20 known negative milk samples to be 2.7mugkg(-1). The detection capability (CCbeta) of the assay was determined to be 5mugkg(-1) for 11 benzimidazole residues and the mean recovery of analytes was in the range 81-116%. A comparison was made between the SPR-biosensor and UPLC-MS/MS analyses of milk samples (n=26) taken from cows treated different benzimidazole products, demonstrating the SPR-biosensor assay to be fit for purpose.

It cannot be all about safety: the benefits of prolonged mobility.

OBJECTIVES: While there is much emphasis on managing the safety of older road users, there is limited understanding and recognition of the significance of mobility and transportation needs, mobility changes in later life, and the impact of reduced mobility on quality of life. Moreover, there is little information about the measures that can be taken to increase or at least maintain mobility in older age. METHOD: A systematic literature review was undertaken to address the issues associated with the transportation and mobility needs of older road users. Articles and publications were selected for relevance and research strength and strategies and measures aimed to manage the safe mobility of older road users were reviewed. RESULTS AND DISCUSSION: The review provides clear evidence that, for older adults who cease driving, quality of life is reduced and that there are a number of adverse consequences of poor mobility. The misconceptions regarding the risks that older drivers pose on the road and how their safe mobility should be managed are discussed, particularly the implications of current licensing procedures on mobility. Evidence is also presented showing there are subgroups of older adults who are more likely to suffer more pronounced mobility consequences including women and financially disadvantaged groups. Moreover, "best-practice" strategies for maintaining at least some level of mobility for older adults are highlighted in four broad categories: safer road users, safer vehicles, safer roads and infrastructure, and provision of new and innovative alternative transport options that are specifically tailored to older adults. CONCLUSIONS: Provision of safe travel options that allow easy access to services and amenities is a vital factor in maintaining mobility amongst older road users. An understanding that continued mobility means access to a private vehicle, either as a driver (for as long as possible as it is safe to drive) or as a passenger, and easy and practical access to other forms of transport is essential in the management of health, well-being, and the safe mobility of older road users.

Teaching young children to cross roads safely.

Road safety education is considered essential to teach children to interact with traffic safely. Many programs, however, do not consider the separate component skills of the road-crossing task, the functional and behavioural factors that may put some children at increased risk, and the most beneficial methods to transfer knowledge to improved behaviour in real-world environments. A targeted and practical training program using a simulated road environment has been developed and evaluated amongst primary school children using a randomised controlled trial. Significant reductions in proportion of critically incorrect road-crossing responses were found immediately after training (56%) and one-month post-training (47%) by the case group compared with pre-training responses, and relative to any changes in responses of the control group. The beneficial effects were greater for younger children, females, children with less well developed perceptual, attentional and cognitive skills, and those with little traffic exposure. The effects of the training program on other outcome measures (proportion of missed opportunity responses, decision time and safety rating responses) were less clear but showed some beneficial effects. This paper discusses the use of the simulated training program, a novel and safe way, to improve road crossing decisions. It is suggested that improvements can be made to child pedestrian education by providing tailored and practical programs that target the component skills of road-crossing decisions and improve essential skills through intensive training and feedback on known risk factors.