Epstein-Barr virus as a marker of survival after Hodgkin's lymphoma: a population-based study.

PURPOSE: Epstein-Barr virus (EBV) in Hodgkin's lymphoma (HL) cells has been considered as a prognostic marker for this heterogeneous disease, but studies have yielded mixed findings, likely because of selected patient series and failure to acknowledge an effect of age on outcome. This study assessed survival after HL in a population-based cohort large enough to examine the joint effects of EBV with other factors including age, sex, and histologic subtype. PATIENTS AND METHODS: Included were 922 patients with classical HL diagnosed between mid-1988 and 1997 in the Greater San Francisco Bay Area, with archived biopsy specimens assayed for EBV with immunohistochemistry and in situ hybridization. Vital status was followed through December 30, 2003 (median follow-up time, 97 months). Overall and disease-specific survival were analyzed with the Kaplan-Meier method and Cox proportional hazards regression models. RESULTS: In children less than 15 years old, EBV presence was suggestively associated (P = .07) with favorable survival. In adults aged 15 to 44 years, EBV did not affect HL outcome, although a protective effect was suggested. In older adults (45 to 96 years), EBV presence nearly doubled the risk of overall and HL-specific mortality but only for patients with nodular sclerosis (NS) histologic subtype (hazard ratio for death = 2.5; 95% CI, 1.5 to 4.3). CONCLUSION: In HL, EBV tumor cell presence is associated with better survival in young patients and poorer survival in older patients with NS, independent of other factors. Variation in outcome by age and histology could indicate biologically distinct disease entities. Evidence that EBV is a meaningful prognostic marker may have therapeutic relevance.     

Anticoagulant Rodenticides

Anticoagulant pesticides are used widely in agricultural and urban rodent control. The emergence of warfarin-resistant strains of rats led to the introduction of a new group of anticoagulant rodenticides variously referred to as ‘superwarfarins’, ‘single dose’ or ‘long-acting’. This group includes the second generation 4-hydroxycoumarins brodifacoum, bromadiolone, difenacoum, flocoumafen and the indanedione derivatives chlorophacinone and diphacinone. Most cases of anticoagulant rodenticide exposure involve young children and, as a consequence, the amounts ingested are almost invariably small. In contrast, intentional ingestion of large quantities of long-acting anticoagulant rodenticides may cause anticoagulation for several weeks or months. Occupational exposure has also been reported. Anticoagulant rodenticides inhibit vitamin K₁-2,3 epoxide reductase and thus the synthesis of vitamin K and subsequently clotting factors II, VII, IX and X. The greater potency and duration of action of long-acting anticoagulant rodenticides is attributed to their: (i) greater affinity for vitamin K₁-2,3-epoxide reductase; (ii) ability to disrupt the vitamin K₁-epoxide cycle at more than one point; (iii) hepatic accumulation; and (iv) unusually long biological half-lives due to high lipid solubility and enterohepatic circulation. Substantial ingestion produces epistaxis, gingival bleeding, widespread bruising, haematomas, haematuria with flank pain, menorrhagia, gastrointestinal bleeding, rectal bleeding and haemorrhage into any internal organ; anaemia may result. Spontaneous haemoperitoneum has been described. Severe blood loss may result in hypovolaemic shock, coma and death. The first clinical signs of bleeding may be delayed and patients may remain anticoagulated for several days (warfarin) or days, weeks or months (long-acting anticoagulants) after ingestion of large amounts. There are now sufficient data in young children exposed to anticoagulant rodenticides to conclude that routine measurement of the international normalised ratio (INR) is unnecessary. In all other cases, the INR should be measured 36–48 hours post exposure. If the INR is normal at this time, even in the case of long-acting formulations, no further action is required. If active bleeding occurs, prothrombin complex concentrate (which contains factors II, VII, IX and X) 50 units/kg, or recombinant activated factor VII 1.2–4.8mg or fresh frozen plasma 15 mL/kg (if no concentrate is available) and phytomenadione 10mg intravenously (100 µg/kg bodyweight for a child) should be given. If there is no active bleeding and the INR is ≤4.0, no treatment is required; if the INR is ≥4.0 phytomenadione 10mg should be administered intravenously.     

Feasibility and acceptability of a motivational interviewing breastfeeding peer support intervention

An uncontrolled study with process evaluation was conducted in three U.K. community maternity sites to establish the feasibility and acceptability of delivering a novel breastfeeding peer‐support intervention informed by motivational interviewing (MI; Mam‐Kind). Peer‐supporters were trained to deliver the Mam‐Kind intervention that provided intensive one‐to‐one peer‐support, including (a) antenatal contact, (b) face‐to‐face contact within 48 hr of birth, (c) proactive (peer‐supporter led) alternate day contact for 2 weeks after birth, and (d) mother‐led contact for a further 6 weeks. Peer‐supporters completed structured diaries and audio‐recorded face‐to‐face sessions with mothers. Semistructured interviews were conducted with a purposive sample of mothers, health professionals, and all peer‐supporters. Interview data were analysed thematically to assess intervention acceptability. Audio‐recorded peer‐support sessions were assessed for intervention fidelity and the use of MI techniques, using the MITI 4.2 tool. Eight peer‐supporters delivered the Mam‐Kind intervention to 70 mothers in three National Health Service maternity services. Qualitative interviews with mothers (n = 28), peer‐supporters (n = 8), and health professionals (n = 12) indicated that the intervention was acceptable, and health professionals felt it could be integrated with existing services. There was high fidelity to intervention content; 93% of intervention objectives were met during sessions. However, peer‐supporters reported difficulties in adapting from an expert‐by‐experience role to a collaborative role. We have established the feasibility and acceptability of providing breastfeeding peer‐support using a MI‐informed approach. Refinement of the intervention is needed to further develop peer‐supporters' skills in providing mother‐centred support. The refined intervention should be tested for effectiveness in a randomised controlled trial.     

Versatility in multiple mini-interview implementation: Rater background does not significantly influence assessment scoring

Abstract

The medical school admissions process seeks to assess a core set of cognitive and non-cognitive competencies that reflect professional readiness and institutional mission alignment. The standardized format of multiple mini-interviews (MMIs) can enhance assessments, and thus many medical schools have switched to this for candidate interviews. However, because MMIs are resource-intensive, admissions deans use a variety of interviewers from different backgrounds/professions. Here, we analyze the MMI process for the 2018 admissions cycle at the VCU School of Medicine, where 578 applicants were interviewed by 126 raters from five distinct backgrounds: clinical faculty, basic science faculty, medical students, medical school administrative staff, and community members. We found that interviewer background did not significantly influence MMI evaluative performance scoring, which eliminates a potential concern about the consistency and reliability of assessment.     

Zero-order release and bioavailability enhancement of poorly water soluble Vinpocetine from self-nanoemulsifying osmotic pump tablet

Abstract

Solid self-nanoemulsifying (S-SNEDDS) asymmetrically coated osmotic tablets of the poorly water-soluble drug Vinpocetine (VNP) were designed. The aim was to control the release of VNP by the osmotic technology taking advantage of the solubility and bioavailability-enhancing capacity of S-SNEDDS. Liquid SNEDDS loaded with 2.5?mg VNP composed of Maisine? 35-1, Transcutol^® HP, and Cremophor^® EL was adsorbed on the solid carrier Aeroperl^®. S-SNEDDS was mixed with the osmotic tablet excipients (sodium chloride, Avicel^®, HPMC-K4M, PVP-K30, and Lubripharm^®), then directly compressed to form the core tablet. The tablets were dip coated and mechanically drilled. A 3²*2¹ full factorial design was adopted. The independent variables were: type of coating material (X₁), concentration of coating solution (X₂), and number of drills (X₃). The dependent variables included % release at 2?h (Y₁), at 4?h (Y₂), and at 8?h (Y₃). The in vivo performance of the optimum formula was assessed in rabbits. Zero-order VNP release was obtained by the single drilled 1.5% Opadry^® CA coated osmotic tablets and twofold increase in VNP bioavailability was achieved. The combination of SNEDDS and osmotic pump tablet system was successful in enhancing the solubility and absorption of VNP as well as controlling its release.     

The Five Factor Model of personality applied to adults who stutter

Previous research has not explored the Five Factor Model of personality among adults who stutter. Therefore, the present study investigated the five personality domains of Neuroticism, Extraversion, Openness, Agreeableness and Conscientiousness, as measured by the NEO Five Factor Inventory (NEO-FFI), in a sample of 93 adults seeking speech treatment for stuttering, and compared these scores with normative data from an Australian and a United States sample. Results revealed that NEO-FFI scores for the stuttering group were within the ‘average’ range for all five personality domains. However, adults who stutter were characterized by significantly higher Neuroticism, and significantly lower Agreeableness and Conscientiousness, than normative samples. No significant differences were found between groups on the dimensions of Extraversion and Openness. These results are discussed with reference to the relationship between personality factors among adults who stutter, their directionality, and implications for predicting treatment outcome.Learning outcomes: The reader will be able to: (1) describe the Five Factor Model of personality, including the NEO-FFI personality domains of Extraversion, Neuroticism, Openness, Agreeableness, and Conscientiousness, and (2) discuss differences in NEO-FFI domain scores between adults who stutter and normative samples, and (3) understand the clinical implications of personality profiles in terms of treatment process and outcome for adults who stutter.     

Prognostic factors associated with survival in patients with hepatocellular carcinoma undergoing transarterial chemoembolisation: an Australian multicenter cohort study

Aim: Transarterial chemoembolisation (TACE) is recommended therapy for intermediate-stage hepatocellular carcinoma (HCC). However, the wide variations in outcom...     

Nucleic Acid Preservation Card Surveillance Is Effective for Monitoring Arbovirus Transmission on Crocodile Farms and Provides a One Health Benefit to Northern Australia

The Kunjin strain of West Nile virus (WNV_KUN) is a mosquito-transmitted flavivirus that can infect farmed saltwater crocodiles in Australia and cause skin lesions that devalue the hides of harvested animals. We implemented a surveillance system using honey-baited nucleic acid preservation cards to monitor WNV_KUN and another endemic flavivirus pathogen, Murray Valley encephalitis virus (MVEV), on crocodile farms in northern Australia. The traps were set between February 2018 and July 2020 on three crocodile farms in Darwin (Northern Territory) and one in Cairns (North Queensland) at fortnightly intervals with reduced trapping during the winter months. WNV_KUN RNA was detected on all three crocodile farms near Darwin, predominantly between March and May of each year. Two of the NT crocodile farms also yielded the detection of MVE viral RNA sporadically spread between April and November in 2018 and 2020. In contrast, no viral RNA was detected on crocodile farms in Cairns during the entire trapping period. The detection of WNV_KUN and MVEV transmission by FTA^TM cards on farms in the Northern Territory generally correlated with the detection of their transmission to sentinel chicken flocks in nearby localities around Darwin as part of a separate public health surveillance program. While no isolates of WNV_KUN or MVEV were obtained from mosquitoes collected on Darwin crocodile farms immediately following the FTA^TM card detections, we did isolate another flavivirus, Kokobera virus (KOKV), from Culex annulirostris mosquitoes. Our studies support the use of the FTA^TM card system as a sensitive and accurate method to monitor the transmission of WNV_KUN and other arboviruses on crocodile farms to enable the timely implementation of mosquito control measures. Our detection of MVEV transmission and isolation of KOKV from mosquitoes also warrants further investigation of their potential role in causing diseases in crocodiles and highlights a “One Health” issue concerning arbovirus transmission to crocodile farm workers. In this context, the introduction of FTA^TM cards onto crocodile farms appears to provide an additional surveillance tool to detect arbovirus transmission in the Darwin region, allowing for a more timely intervention of vector control by relevant authorities.