Molecular characterization and phylogenetic analysis of Marek's disease virus in chickens from Ogun State, Nigeria.

Marek's disease (MD) is caused by oncogenic MD virus serotype 1 (MDV1) and is characterized by lymphoproliferative lesions resulting in high morbidity and mortality in chickens. Despite being ubiquitous on poultry farms, there is a dearth of information on its molecular characteristics in Nigeria. This study aimed at characterizing three virulence genes (Meq, pp38, and vIL-8) of MDV1 from chickens in Ogun state, Nigeria. Blood, feather quill, and tumour samples of chickens from different commercial poultry farms in Ogun State were pooled, spotted on 107 FTA cards, and screened for MDV1 by polymerase chain reaction (PCR). Phylogenetic analysis was carried out to compare Nigerian MDV1 Meq, pp38, and vIL-8 genes sequences with the published references. Thirteen samples were MDV1-positive and the Meq, as well as pp38, and vIL-8 genes from the different samples were 100% identical. The Meq genes contained 339 amino acids (aa) with three PPPP motifs in the transactivation domain and two interruptions of the PPPP motifs due to proline-to-arginine substitutions at positions 176 and 217 resulting in a 20.88% proline composition. Phylogenetic analysis revealed that the Meq gene clustered with strains from Egypt and very virulent ATE2539 strain from Hungary. Mutations were observed in the pp38 protein (at positions 107 and 109) and vIL-8 protein (at positions 4 and 31). Based on the molecular analysis of the three genes, the results indicate the presence of MDV1 with virulence signatures; therefore, further studies on in vivo pathotyping of Nigerian MDV1 from all states should be performed.RESEARCH HIGHLIGHTS Meq, pp38 and vIL-8 genes were 100% identical between Nigerian MDV strains.Proline content in Nigerian meq gene was 20.88% with two PPPP motifs interruptions.Meq, pp38 and vIL-8 genes of Nigerian MDV were similar to Egyptian and Indian strains.

The frequency of change in five-point scale score with a Bayesian penalised likelihood PET reconstruction algorithm on interim FDG PET-CT and its potential implications for therapy decisions in Hodgkin's lymphoma.

AIM: To assess the effect of a Bayesian penalised likelihood (BPL) reconstruction algorithm on the five-point scale (5-PS) score, response categorisation, and potential implications for therapy decisions after interim 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET)-computed tomography (CT) (iPET-CT) to guide treatment in classical Hodgkin's lymphoma (HL). MATERIALS AND METHODS: The present study included new patients with HL undergoing iPET-CT from 2014-2019 after two cycles of doxorubicin (Adriamycin), bleomycin, vincristine, and dacarbazine (ABVD). Two reporters categorised response using the 5-PS and measured maximum standardised uptake values (SUVmax) of the most avid tumour residuum, mediastinal blood pool, and normal liver with ordered subset expected maximisation (OSEM) and BPL reconstructions. RESULTS: Eighty-one iPET-CT examinations were reviewed. Compared with OSEM, BPL increased the 5-PS score by a single score in 18/81 (22.2%) patients. The frequency of potential treatment intensification by changing a score of 3-4 was 13.6% (11/81) and represented 25% (11/44) of patients with a score of 3 on OSEM. All 11 patients remained in remission without a change in therapy (mean 63 months) except one who required second-line treatment for refractory disease. Median SUVmax of tumour residuum was significantly higher with BPL compared with OSEM (2.7 versus 2.4, p<<0.0001), whilst liver SUVmax was significantly lower for both reporters (up to 6.6%, p<0.0001). CONCLUSION: BPL PET reconstruction increased the 5-PS score on iPET-CT in 22% of HL patients and can potentially result in unnecessary treatment escalation in over half of these patients.

Multiple staging investigations may not change management in patients with high-grade dysplasia or early esophageal adenocarcinoma.

The clinical value of multiple staging investigations for high-grade dysplasia or early adenocarcinoma of the esophagus is unclear. A single-center prospective cohort of patients treated for early esophageal cancer between 2000 and 2019 was analyzed. This coincided with a transition period from esophagectomy to endoscopic mucosal resection (EMR) as the treatment of choice. Patients were staged with computed tomography (CT), endoscopic ultrasound (EUS) and 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography(PET)/CT. The aim of this study was to assess their accuracy and impact on clinical management. 297 patients with high-grade dysplasia or early adenocarcinoma were included (endoscopic therapy/EMR n = 184; esophagectomy n = 113 [of which a 'combined' group had surgery preceded by endoscopic therapy n = 23]). Staging accuracy was low (accurate staging EMR: CT 40.1%, EUS 29.6%, FDG-PET/CT 11.0%; Esophagectomy: CT 43.3%, EUS 59.7%, FDG-PET/CT 29.6%; Combined: CT 28.6%, EUS46.2%, FDG-PET/CT 30.0%). Staging inaccuracies across all groups that could have changed management by missing T2 disease were CT 12%, EUS 12% and FDG-PET/CT 1.6%. The sensitivity of all techniques for detecting nodal disease was low (CT 12.5%, EUS 12.5%, FDG-PET/CT0.0%). Overall, FDG-PET/CT and EUS changed decision-making in only 3.2% of patients with an early cancer on CT and low-risk histology. The accuracy of staging with EUS, CT and FDG-PET/CT in patients with high-grade dysplasia or early adenocarcinoma of the esophagus is low. EUS and FDG-PET/CT added relevant staging information over standard CT in very few cases, and therefore, these investigations should be used selectively. Factors predicting the need for esophagectomy are predominantly obtained from EMR histology rather than staging investigations.

Reduced Cerebrovascular Oxygenation in Individuals with Post-Acute COVID-19 Syndrome (PACS) ("long COVID").

There is evidence that hypoxia occurs in the brain of some individuals who contracted the COVID-19 disease. Furthermore, it has been widely reported that about 13% of individuals who contracted the COVID-19 disease report persistent symptoms after the acute infection stage (>2 months post-acute infection). This is termed post-acute COVID-19 syndrome (PACS) or ("long COVID"). In this study, we aimed to determine if hypoxia measured non-invasively with frequency domain near-infrared spectroscopy (fdNIRS) occurs in asymptomatic and symptomatic individuals with post-acute COVID-19 disease. We show that 26% of our symptomatic group, measured on average 9.6 months post-acute COVID-19 disease, were hypoxic and 12% of the asymptomatic group, measured on average 2.5 months post-acute infection, were hypoxic. Our study indicates that fdNIRS measure of hypoxia in the brain may be a useful tool to identify individuals that are likely to respond to treatments targeted at reducing inflammation and improving oxygenation.

Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103+ immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials.

BACKGROUND: High CD103+ intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis. PATIENTS AND METHODS: We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103+ ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial. RESULTS: Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103+ ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio = 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS. CONCLUSIONS: CD103+ ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials.

Multicenter Evaluation of the Simplexa VZV Direct Assay for Detection of Varicella-Zoster Virus in Cerebrospinal Fluid and Lesion-Swab Specimens.

Varicella-zoster virus (VZV) is the etiologic agent of varicella (chickenpox) and herpes zoster (shingles) infections commonly involving skin, mucous membranes, and less frequently the central nervous system. Traditional methods for the laboratory diagnosis of these infections are time-consuming, labor-intensive, and often insensitive. As such, these tests are being replaced by more sensitive and rapid molecular methods. This study evaluated the performance of two different molecular assays, the Simplexa VZV Direct and Simplexa VZV Swab Direct, to detect VZV DNA in cerebrospinal fluid (CSF) and lesion-swab specimens, respectively. The Simplexa VZV Direct and Simplexa VZV Swab Direct assays were compared against individual composite reference methods that varied depending on the sample cohort examined. A total of 883 CSF and 452 cutaneous and mucocutaneous prospective, retrospective, and contrived specimens were evaluated in this multicenter study. The results of this study showed that the Simplexa assays demonstrated near perfect agreement (k = 0.98) compared to the composite reference methods for the detection of VZV in CSF and lesion swab specimens. A further comparison between the standard of care molecular assays employed at the site of specimen collection and the Simplexa assays demonstrated excellent agreement (k = 1.0). The Simplexa assays offer rapid and reliable alternatives for the detection of VZV in certain clinical specimens without the need for nucleic acid extraction.

NB housing study protocol: investigating the relationship between subsidized housing, mental health, physical health and healthcare use in New Brunswick, Canada.

BACKGROUND: Income and housing are pervasive social determinants of health. Subsidized housing is a prominent affordability mechanism in Canada; however, waitlists are lengthy. Subsidized rents should provide greater access to residual income, which may theoretically improve health outcomes. However, little is known about the health of tenants who wait for and receive subsidized housing. This is especially problematic for New Brunswick, a Canadian province with low population density, whose inhabitants experience income inequality, social exclusion, and challenges with healthcare access.  METHODS: This study will use a longitudinal, prospective matched cohort design. All 4,750 households on New Brunswick's subsidized housing wait list will be approached to participate. The survey measures various demographic, social and health indicators at six-month intervals for up to 18 months as they wait for subsidized housing. Those who receive housing will join an intervention group and receive surveys for an additional 18 months post-move date. With consent, participants will have their data linked to a provincial administrative database of medical records.  DISCUSSION: Knowledge of housing and health is sparse in Canada. This study will provide stakeholders with a wealth of health information on a population that is historically under-researched and underserved.

Non-invasive Detection of Persistent Cortical Hypoxia in Multiple Sclerosis Using Frequency Domain Near-Infrared Spectroscopy (fdNIRS).

There may be a relationship between hypoxia and inflammation, which is important in the outcomes of a wide array of human diseases. Multiple sclerosis (MS) is one such disease. There is evidence that hypoxia may influence inflammation in MS. We showed previously that about 40% of participants with MS had hypoxia in the cortical grey matter using frequency-domain near-infrared spectroscopy (fdNIRS). In this study, we aimed to determine if hypoxia in MS persists chronically (for a year or more) by measuring at baseline and ≥12 months later. We found that hypoxia persists for at least a year in 80% of participants with MS. As more individuals remained hypoxic than returned to normoxia, the development of hypoxia may relate to disease progression.

Characterizing the literature surrounding transportation of young dairy calves: A scoping review.

Transportation is a stressful event for cattle, as it may involve various handling practices, commingling, deprivation of food and water, and fluctuating temperatures. Calves are particularly susceptible to these stressors because their physiological and immune systems are still developing. There has been no formal synthesis of the scientific literature evaluating the effect of transportation on young dairy calf health and performance; the aim of this scoping review is to describe and characterize this body of work. We targeted both descriptive and analytic studies examining transport of calves, including listing how the effect of transport has been evaluated. Eight databases were searched for relevant articles with eligible studies being primary research articles investigating transportation of calves of either sex who were younger than 60 d of age or weighed less than 100 kg. Two reviewers independently screened the title and abstracts of 6,859 articles with 361 potentially relevant articles screened at full text. Of these, 46 were relevant and had data extracted. Articles reporting study location were conducted in the United States (n = 5), Australia (n = 3), Japan (n = 3), and New Zealand (n = 3). Common transport-related variables evaluated included time in transit (n = 13), distance of transportation (n = 8), vehicle-related factors (n = 8), and age at time of transportation (n = 4). Outcome measures varied greatly, including blood parameters (n = 28), health assessments (n = 20), weight (n = 17), behavioral metrics (n = 14), mortality (n = 7), feed intake following transportation (n = 4), salivary cortisol concentrations (n = 3), morbidity (n = 3), and isolation of Salmonella Dublin in fecal samples (n = 2). Outcome parameters were measured during transport or ranged from immediately after to one year following transportation. As the transport-related risk factors and outcomes measured assessed varied widely between studies, future quantitative synthesis (e.g., meta-analysis) in this area may be limited. Several knowledge gaps were identified, including methods to prepare calves for transportation, such as improving nutrition, administering medication, or transporting calves at an older age or weight. Further research could also focus on consistent and clear reporting of key items related to study conduct and analysis, as well as the development of a core outcome set for calf transport studies.

Near-Infrared Spectroscopy Reveals Brain Hypoxia and Cerebrovascular Dysregulation in Primary Biliary Cholangitis.

BACKGROUND AND AIMS: Primary biliary cholangitis (PBC) is an autoimmune cholestatic liver disease linked to symptoms including fatigue and altered mood/cognition, indicating that chronic liver inflammation associated with PBC can impact brain function. We employed near-infrared spectroscopy (NIRS), a noninvasive neuroimaging technique, to determine whether patients with PBC exhibit reduced cerebral oxygen saturation (StO2 ) and altered patterns of microvascular cerebral blood perfusion and whether these alterations were associated with clinical phenotype. This observational case-control study was conducted at a tertiary hospital clinic (University of Calgary Liver Unit). APPROACH AND RESULTS: Thirteen female patients with noncirrhotic PBC, seven female patients with cirrhotic PBC, and 11 healthy female controls were recruited by physician referral and word of mouth, respectively. NIRS was used to measure cerebral hemoglobin and oxygen saturation. A wavelet phase coherence method was used to estimate the coherent frequency coupling of temporal changes in cerebral hemodynamics. The PBC group demonstrated significantly reduced cerebral StO2 (P = 0.01, d = 0.84), indicating cerebral hypoxia, significantly increased cerebral deoxygenated hemoglobin concentration (P < 0.01, d = 0.86), and significantly reduced hemodynamic coherence in the low-frequency band (0.08-0.15 Hz) for oxygenated hemoglobin concentration (P = 0.02, d = 0.99) and total hemoglobin (tHb) concentration (P = 0.02, d = 0.50), indicating alterations in cerebrovascular activity. Complete biochemical response to ursodeoxycholic acid (UDCA) therapy in early patients with PBC was associated with increased cerebral tHb concentration and decreased hemodynamic coherence. CONCLUSIONS: Using NIRS, patients with PBC were found to have hypoxia, increased cerebral hemoglobin concentration, and altered cerebrovascular activity, which were reversed in part in UDCA responders. In addition, symptoms and quality-of-life measures did not correlate with brain hypoxia or cerebrovascular dysregulation in patients with PBC.

The potential utility of abbreviated breast MRI (FAST MRI) as a tool for breast cancer screening: a systematic review and meta-analysis.

AIM: To synthesise evidence comparing abbreviated breast magnetic resonance imaging (abMRI) to full-protocol MRI (fpMRI) in breast cancer screening. MATERIALS AND METHODS: A systematic search was undertaken in multiple databases. Cohort studies without enrichment, presenting accuracy data of abMRI in screening, for any level of risk (population, moderate, high risk) were included. Level of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Meta-analyses (bivariate random effects model) were performed for abMRI, with fpMRI and histology from fpMRI-positive cases as reference standard, and with follow-up to symptomatic detection added to the fpMRI. The review also covers evidence comparing abMRI with mammographic techniques. RESULTS: The title and abstract review retrieved 23 articles. Five studies (six articles) were included (2,763 women, 3,251 screening rounds). GRADE assessment of the evidence was very low because the reference standard was interpreted with knowledge of the index test and biopsy was not obtained for all abMRI positives. The overall sensitivity for abMRI, with fpMRI (and histology for fpMRI positives) as reference standard, was 94.8% (95% confidence interval [CI] 85.5-98.2) and specificity as 94.6% (95% CI: 91.5-96.6). Three studies (1,450 women, 1,613 screening rounds) presented follow-up data, enabling comparison between abMRI and fpMRI. Sensitivities and specificities for abMRI did not differ significantly from those for fpMRI (p=0.83 and p=0.37, respectively). CONCLUSION: A very low level of evidence suggests abMRI could be accurate for breast cancer screening. Research is required, with follow-up to interval cancer, to determine the effect its use could have on clinical outcome.

Palatine tonsil SUVmax on FDG PET-CT as a discriminator between benign and malignant tonsils in patients with and without head and neck squamous cell carcinoma of unknown primary.

AIM: To analyse the maximum standardised uptake value (SUVmax) ratio between tonsils in patients with and without tonsillar carcinoma to determine useful diagnostic thresholds. MATERIALS AND METHODS: Positron-emission tomography (PET)/computed tomography (CT) examinations of patients with suspected head and neck squamous cell carcinoma (SCC) and controls from April 2013 to September 2016 were reviewed retrospectively. Tonsillar SUVmax ratios (ipsilateral/contralateral for malignant tonsils, maximum/minimum for patients without [controls]) were calculated and used to construct a receiver operating characteristic (ROC) curve. RESULTS: Twenty-five patients had tonsillar carcinoma (mean SUVmax ratio of 2, range 0.89-5.4) and 86 patients acted as controls (mean SUVmax ratio of 1.1, range 1-1.5). Using the ROC, the most accurate SUVmax ratio for identifying malignancy was >1.2 (77% sensitivity, 86% specificity). A potentially more clinically useful SUVmax ratio is ≥1.6 with 62% sensitivity and 100% specificity. CONCLUSION: An SUVmax ratio between tonsils of ≥1.6 is highly suspicious for SCC and could be used to direct site of biopsy. Some malignant tonsils had normal FDG uptake; therefore, PET/CT should not be used to exclude tonsillar cancer. Minor asymmetrical uptake is frequently seen in non-malignant tonsils and does not necessarily require further investigation. Due to the single centre nature of this study and the recognised variation in SUV measurements between PET scans, other centres may need to develop their own cut-offs.

Choice test to determine potential attractants and repellents for the sheep scab mite, Psoroptes ovis (Acari: Psoroptidae).

A choice test bioassay was devised to screen compounds as potential semiochemicals (e.g., kairomones or allomones that mediate aggregation, attraction or repellence) for the obligate parasitic mite, Psoroptes ovis. The choice test used filter paper discs in a 1:4 test:control ratio and was found to be a reliable, effective and efficient method. Four mammalian lipid components were assessed as potential attractants-linoleic acid, arachidonic acid, methyl myristate and squalene-, and the insect/tick repellent DEET for potential repellence. Linoleic acid was significantly attractive to P. ovis adult females and has the potential to act as an attractant. Identification of P. ovis semiochemicals, especially attractants, would be beneficial in the development of novel control methods and tools for this species. This is essential considering the increase in resistance to the limited prophylactic chemical treatments in the UK, and the high prevalence of scab infections.

Circulating tumor DNA predicts survival in patients with resected high-risk stage II/III melanoma.

Background: Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma. Patients and methods: We carried out droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial. Results: Mutant BRAF or NRAS ctDNA was detected (≥1 copy of mutant ctDNA) in 15/132 (11%) BRAF mutant patient samples and 4/29 (14%) NRAS mutant patient samples. Patients with detectable ctDNA had a decreased disease-free interval [DFI; hazard ratio (HR) 3.12; 95% confidence interval (CI) 1.79-5.47; P < 0.0001] and distant metastasis-free interval (DMFI; HR 3.22; 95% CI 1.80-5.79; P < 0.0001) versus those with undetectable ctDNA. Detectable ctDNA remained a significant predictor after adjustment for performance status and disease stage (DFI: HR 3.26, 95% CI 1.83-5.83, P < 0.0001; DMFI: HR 3.45, 95% CI 1.88-6.34, P < 0.0001). Five-year overall survival rate for patients with detectable ctDNA was 33% (95% CI 14%-55%) versus 65% (95% CI 56%-72%) for those with undetectable ctDNA. Overall survival was significantly worse for patients with detectable ctDNA (HR 2.63; 95% CI 1.40-4.96); P = 0.003) and remained significant after adjustment for performance status (HR 2.50, 95% CI 1.32-4.74, P = 0.005). Conclusion: ctDNA predicts for relapse and survival in high-risk resected melanoma and could aid selection of patients for adjuvant therapy. Clinical trial number: ISRCTN 81261306.

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Background: Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods: Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results: Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56 years (range 18-88 years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5 years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P = 0.78). At 5 years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P = 0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P = 0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P = 0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P = 0.21). Conclusions: Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information: ISRCTN 81261306; EudraCT Number: 2006-005505-64.

Epidemiology and risk factors for hepatitis C virus infection in a high-prevalence population.

To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case-control study among persons who use drugs. During June-October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case-control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1-51.9), IDU alone (aOR 52.7, CI 25.3-109.9), intranasal drug use alone (aOR 2.6, CI 1.8-3.9) and incarceration (aOR 2.7, CI 2.0-3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1-18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.

Advocacy, support and survivorship in prostate cancer.

Across Australia, prostate cancer support groups (PCSG) have emerged to fill a gap in psychosocial care for men and their families. However, an understanding of the triggers and influencers of the PCSG movement is absent. We interviewed 21 SG leaders (19 PC survivors, two partners), of whom six also attended a focus group, about motivations, experiences, past and future challenges in founding and leading PCSGs. Thematic analysis identified four global themes: illness experience; enacting a supportive response; forming a national collective and challenges. Leaders described men's feelings of isolation and neglect by the health system as the impetus for PCSGs to form and give/receive mutual help. Negotiating health care systems was an early challenge. National affiliation enabled leaders to build a united voice in the health system and establish a group identity and collective voice. Affiliation was supported by a symbiotic relationship with tensions between independence, affiliation and governance. Future challenges were group sustainability and inclusiveness. Study findings describe how a grassroots PCSG movement arose consistent with an embodied health movement perspective. Health care organisations who seek to leverage these community resources need to be cognisant of SG values and purpose if they are to negotiate effective partnerships that maximise mutual benefit.

'Care and Prevent': rationale for investigating skin and soft tissue infections and AA amyloidosis among people who inject drugs in London.

BACKGROUND: Skin and soft tissue infections (SSTIs) are a leading cause of morbidity and mortality among people who inject drugs (PWID). International data indicate up to one third of PWID have experienced an SSTI within the past month. Complications include sepsis, endocarditis and amyloid A (AA) amyloidosis. AA amyloidosis is a serious sequela of chronic SSTI among PWID. Though there is a paucity of literature reporting on AA amyloidosis among PWID, what has been published suggests there is likely a causal relationship between AA amyloidosis and injecting-related SSTI. If left untreated, AA amyloidosis can lead to renal failure; premature mortality among diagnosed PWID is high. Early intervention may reverse disease. Despite the high societal and individual burden of SSTI among PWID, empirical evidence on the barriers and facilitators to injecting-related SSTI prevention and care or the feasibility and acceptability of AA amyloidosis screening and treatment referral are limited. This study aims to fill these gaps and assess the prevalence of AA amyloidosis among PWID. METHODS: Care and Prevent is a UK National Institute for Health Research-funded mixed-methods study. In five phases (P1-P5), we aim to assess the evidence for AA amyloidosis among PWID (P1); assess the feasibility of AA amyloidosis screening, diagnostic and treatment referral among PWID in London (P2); investigate the barriers and facilitators to AA amyloidosis care (P3); explore SSTI protection and risk (P4); and co-create harm reduction resources with the affected community (P5). This paper describes the conceptual framework, methodological design and proposed analysis for the mixed-methods multi-phase study. RESULTS: We are implementing the Care and Prevent protocol in London. The systematic review component of the study has been completed and published. Care and Prevent will generate an estimate of AA amyloidosis prevalence among community recruited PWID in London, with implications for the development of screening recommendations and intervention implementation. We aim to recruit 400 PWID from drug treatment services in London, UK. CONCLUSIONS: Care and Prevent is the first study to assess screening feasibility and the prevalence of positive proteinuria, as a marker for AA amyloidosis, among PWID accessing drug treatment services. AA amyloidosis is a serious, yet under-recognised condition for which early intervention is available but not employed.

Discrepancies in central review re-testing of patients with ER-positive and HER2-negative breast cancer in the OPTIMA prelim randomised clinical trial.

BACKGROUND: There is limited data on results of central re-testing of samples from patients with invasive breast cancer categorised in their local hospital laboratories as oestrogen receptor (ER) positive and human epidermal growth factor receptor homologue 2 (HER2) negative. METHODS: The Optimal Personalised Treatment of early breast cancer usIng Multiparameter Analysis preliminary study (OPTIMA prelim) was the feasibility phase of a randomised controlled trial to validate the use of multiparameter assay-directed chemotherapy decisions in the UK National Health Service (NHS). Eligibility criteria included ER positivity and HER2 negativity. Central re-testing of receptor status was mandatory. RESULTS: Of the 431 patients tested centrally, discrepant results between central and local laboratory results were identified in only 19 (4.4%; 95% confidence interval 2.5-6.3%) patients (with 21 tumours). On central review, seven patients had cancers that were ER-negative (1.6%) and 13 (3.0%) patients with 15 tumours had HER2-positive disease, including one tumour discrepant for both biomarkers. CONCLUSIONS: Central re-testing of receptor status of invasive breast cancers in the UK NHS setting shows a high level of reproducibility in categorising tumours as ER-positive and HER2-negative, and raises questions regarding the cost effectiveness and clinical value of central re-testing in this sub-group of breast cancers in this setting.

Disease-free and overall survival at 3.5 years for neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin and cyclophosphamide, for women with HER2 negative early breast cancer: ARTemis Trial.

BACKGROUND: The ARTemis trial previously reported that addition of neoadjuvant bevacizumab (Bev) to docetaxel (D) followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC) in HER2 negative breast cancer improved the pathological complete response (pCR) rate. We present disease-free survival (DFS) and overall survival (OS) with central pathology review. PATIENTS AND METHODS: Patients were randomized to 3 cycles of D followed by 3 cycles of FEC (D-FEC), ±4 cycles of Bev (Bev + D-FEC). DFS and OS were analyzed by treatment and by central pathology reviewed pCR and Residual Cancer Burden (RCB) class. RESULTS: A total of 800 patients were randomized [median follow-up 3.5 years (IQR 3.2-4.4)]. DFS and OS were similar across treatment arms [DFS hazard ratio (HR)=1.18 (95% CI 0.89-1.57), P = 0.25; OS HR = 1.26 (95% CI 0.90-1.76), P = 0.19). Both local pathology report review and central histopathology review confirmed a significant improvement in DFS and OS for patients who achieved a pCR [DFS HR = 0.38 (95% CI 0.23-0.63), P < 0.001; OS HR = 0.43 (95% CI 0.24-0.75), P = 0.003]. However, significant heterogeneity was observed (P = 0.02); larger improvements in DFS were obtained with a pCR achieved with D-FEC than a pCR achieved with Bev + D-FEC. As RCB class increased, significantly worse DFS and OS was observed (P for trend <0.0001), which effect was most marked in the ER negative group. CONCLUSIONS: The addition of short course neoadjuvant Bev to standard chemotherapy did not demonstrate a DFS or OS benefit. Achieving a pCR with D-FEC is associated with improved DFS and OS but not when pCR is achieved with Bev + D-FEC. At the present time therefore, Bev is not recommended in early breast cancer. CLINICALTRIALS.GOV NUMBER: NCT01093235.