Naresuan University Journal
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Current practice and factors influencing the provision of periodontal healthcare in primary dental care in Scotland: an explorative study.
No full textAIMS: To understand current practice and the beliefs of dentists and hygienists towards factors which may influence the management of patients with periodontal diseases in primary dental care in Scotland. To inform the scope of a guidance publication and the future development of diagnostic analyses tools. METHODS: A qualitative approach of semi-structured telephone interviews with a randomly selected sample of dentists and hygienists was used. Interviews continued until saturation was reached and were audio-recorded and transcribed verbatim. The data were analysed using the method of framework analysis. To increase the participation of hygienists the topic guide was adapted into a self-reporting questionnaire and posted to all hygienists in Scotland. RESULTS: Eighteen dentists and three hygienists were interviewed. Key themes identified were extent of control over working environment, capabilities to treat appropriately and changing patients' oral hygiene behaviour. Factors which facilitated the management of patients with periodontal diseases were 'access to a hygienist' and 'beliefs about capabilities', while 'routine and habit', 'motivation of patients' and 'time and money' were perceived as barriers. Some evidence of variation in treatment provision and of varying levels of confidence among practitioners about treating more advanced periodontal conditions was identified. Two hundred and thirty-seven hygienists returned the postal questionnaire. Agreement was found with the views of the interviewed hygienists on beliefs about capabilities and routine record-keeping. CONCLUSION: To improve the periodontal health of patients requires consideration of both extrinsic and intrinsic factors present in primary dental care. Practitioners would find having guidance on managing patients with basic periodontal examinations of three and four, referral criteria to secondary care, record-keeping and techniques to change patients' oral hygiene behaviour particularly useful. Applying the evaluative framework pre-publication indicated where knowledge translation interventions may be required in the future
Mät inte effektivitet – mät hälsa och glädje [Do not measure effectiveness - measure health and happiness]
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HLA-DRB1*11 and variants of the MHC class II locus are strong risk factors for systemic juvenile idiopathic arthritis.
No full textSystemic juvenile idiopathic arthritis (sJIA) is an often severe, potentially life-threatening childhood inflammatory disease, the pathophysiology of which is poorly understood. To determine whether genetic variation within the MHC locus on chromosome 6 influences sJIA susceptibility, we performed an association study of 982 children with sJIA and 8,010 healthy control subjects from nine countries. Using meta-analysis of directly observed and imputed SNP genotypes and imputed classic HLA types, we identified the MHC locus as a bona fide susceptibility locus with effects on sJIA risk that transcended geographically defined strata. The strongest sJIA-associated SNP, rs151043342 [P = 2.8 × 10(-17), odds ratio (OR) 2.6 (2.1, 3.3)], was part of a cluster of 482 sJIA-associated SNPs that spanned a 400-kb region and included the class II HLA region. Conditional analysis controlling for the effect of rs151043342 found that rs12722051 independently influenced sJIA risk [P = 1.0 × 10(-5), OR 0.7 (0.6, 0.8)]. Meta-analysis of imputed classic HLA-type associations in six study populations of Western European ancestry revealed that HLA-DRB1*11 and its defining amino acid residue, glutamate 58, were strongly associated with sJIA [P = 2.7 × 10(-16), OR 2.3 (1.9, 2.8)], as was the HLA-DRB1*11-HLA-DQA1*05-HLA-DQB1*03 haplotype [6.4 × 10(-17), OR 2.3 (1.9, 2.9)]. By examining the MHC locus in the largest collection of sJIA patients assembled to date, this study solidifies the relationship between the class II HLA region and sJIA, implicating adaptive immune molecules in the pathogenesis of sJIA
Target delineation variability and corresponding margins of peripheral early stage NSCLC treated with stereotactic body radiotherapy.
No full textPURPOSE: To quantify the target delineation variability in peripheral early stage lung cancer treated with SBRT and derive corresponding margins. METHODS AND MATERIALS: Sixteen early stage NSCLC GTV's were delineated by 11 radiation oncologists from 4 institutes. A median surface was computed and the delineation variation perpendicular to this surface was measured (local standard deviation=SD). The overall target delineation variability was quantified by the root-mean-square (rms) of the local SD. The required margin was determined by expanding all delineations to encompass the median surface, where after the underlying probability distribution was modeled by a number of uncorrelated 'pimples-and-dimples'. RESULTS: The overall target delineation variability was 2.1mm (rms). Institute I-III delineated significantly smaller volumes than institute IV, yielding target delineation variabilities of 1.2mm and 1.8mm respectively. The margin required to obtain 90% coverage of the delineated contours was 3.4mm and 5.9mm respectively. The factor α in M=αΣ required to calculate adequate margins was 2.8-3.2, which is larger than the 2.5 found for 3D rigid target displacement. CONCLUSION: A relatively small target delineation uncertainty of 1.2mm-1.8mm (1SD) was observed for early stage NSCLC. A 3.4-5.9mm GTV-to-PTV margin was required to account for this uncertainty alone, ignoring other sources of geometric uncertainties
AZD3514, an oral selective androgen receptor down-regulator in patients with castration-resistant prostate cancer - results of two parallel first-in-human phase I studies.
No full textBACKGROUND: AZD3514 is a first-in-class, orally bio-available, androgen-dependent and -independent androgen receptor inhibitor and selective androgen-receptor down-regulator (SARD). METHODS: In study 1 and 2, castration-resistant prostate cancer (CRPC) patients (pts) were initially recruited into a once daily (QD) oral schedule (A). In study 1, pharmacokinetic assessments led to twice daily (BID) dosing (schedule B) to increase exposure. Study 2 explored a once daily schedule. RESULTS: In study 1, 49 pts were treated with escalating doses of AZD3514 (A 35 pts, B 14 pts). Starting doses were 100 mg (A) and 1000 mg (B). The AZD3514 formulation was switched from capsules to tablets at 1000 mg QD. 2000 mg BID was considered non-tolerable due to grade (G) 2 toxicities (nausea [N], vomiting [V]). No adverse events (AEs) met the dose-limiting toxicity (DLT) definition. Thirteen pts received AZD3514 in study 2, with starting doses of 250 mg QD. The most frequent drug-related AEs were N: G1/2 in 55/70 pts (79 %); G3 in 1 pt (1.4 %); & V: G1/2 in 34/70 pts (49 %) & G3 in 1 pt (1.4 %). PSA declines (≥50 %) were documented in 9/70 patients (13 %). Objective soft tissue responses per RECIST1.1 were observed in 4/24 (17 %) pts in study 1. CONCLUSION: AZD3514 has moderate anti-tumour activity in pts with advanced CRPC but with significant levels of nausea and vomiting. However, anti-tumour activity as judged by significant PSA declines, objective responses and durable disease stabilisations, provides the rationale for future development of SARD compounds
