Citations

Objective To analyse the trends in opportunistic PSA screening in A ustralia, focusing on younger men (<55 years of age), to examine the effects of this screening on transrectal ultrasonography ( TRUS )‐guided biopsy rates and to determine the nature of prostate cancers ( PC as) being detected. Subjects and Methods All men who received an opportunistic screening PSA test and TRUS ‐guided biopsy between 2001 and 2008 in A ustralia were analysed using data from the A ustralian C ancer registry ( A ustralian I nstitute of H ealth and W elfare) and Medicare databases. The V ictorian cancer registry was used to obtain G leason scores. Age‐standardized and age‐specific rates were calculated, along with the incidence of PC a, and correlated with G leason scores. Results A total 5 174 031 PSA tests detected 128 167 PC as in the period 2001–2008. During this period, PSA testing increased by 146% (a mean of 4629 tests per 100 000 men annually), with 80 and 59% increases in the rates of TRUS ‐guided biopsy and incidence of PC a, respectively. The highest increases in PSA screening occurred in men <55 years old and up to 1101 men had to be screened to detect one incident case of PC a (0.01%). Screening resulted in two thirds of men aged <55 years receiving a negative TRUS biopsy. There was no correlation with G leason >7 tumours in patients aged <55 years. Conclusion Despite the ongoing controversy about the merits of PCa screening, there was an increase in PSA testing, especially in men <55 years old, leading to a modestly higher incidence of PC a in A ustralia. Overall, PSA screening was associated with high rates of negative TRUS ‐biopsy and the detection of low/intermediate grade PCa among younger patients.

Abstract Background There is growing attention towards increasing patient and service user engagement ( PSUE ) in biomedical and health services research. Existing variations in language and design inhibit reporting and indexing, which are crucial to comparative effectiveness in determining best practices. Objective This paper utilizes a systematic review and environmental scan to derive an evidence‐based framework for PSUE . Design A metanarrative systematic review and environmental scan/manual search using scientific databases and other search engines, along with feedback from a patient advisory group ( PAG ). Eligible sources English‐language studies, commentaries, grey literature and other sources (including systematic and non‐systematic reviews) pertaining to patient and public involvement in biomedical and health services research. Data extracted Study description (e.g. participant demographics, research setting) and design, if applicable; frameworks, conceptualizations or planning schemes for PSUE ‐related endeavours; and methods for PSUE initiation and gathering patients'/service users' input or contributions. Results Overall, 202 sources were included and met eligibility criteria; 41 of these presented some framework or conceptualization of PSUE . Sources were synthesized into a two‐part framework for PSUE: (i) integral PSUE components include patient and service user initiation, reciprocal relationships, colearning and re‐assessment and feedback, (ii) sources describe PSUE at several research stages, within three larger phases: preparatory, execution and translational. Discussion and Conclusions Efforts at developing a solid evidence base on PSUE are limited by the non‐standard and non‐empirical nature of much of the literature. Our proposed two‐part framework provides a standard structure and language for reporting and indexing to support comparative effectiveness and optimize PSUE .

Objective Preclinical evaluation of headache by behavioral assessment of reward from pain relief. Methods Inflammatory mediators (IMs) or control solution were applied to the rat dura mater to elicit a presumed state of cephalic pain. Hind paw incision was used in separate groups of animals to model noncephalic postsurgical pain. Drugs were given systemically or microinjected within the rostral ventromedial medulla (RVM), nucleus accumbens (NAc), or rostral anterior cingulate cortex (rACC). Peripheral nerve block was produced at the level of the popliteal fossa, and behavior was assessed using evoked sensory stimuli or conditioned place preference (CPP). Immunohistochemistry and brain microdialysis measurements were performed. Results Dural IMs produced long‐lasting generalized cutaneous allodynia. RVM lidocaine produced CPP, increased NAc c‐Fos, and dopamine release selectively in rats receiving dural IMs; CPP was blocked by intra‐NAc α‐flupenthixol, a dopaminergic antagonist. Intravenous α‐calcitonin gene‐related peptide (αCGRP) (8–37) produced CPP and elicited NAc dopamine release selectively in rats treated with dural IMs. Prior lesion of the rACC or treatment with systemic sumatriptan or αCGRP (8–37) abolished RVM lidocaine‐induced CPP in IM‐treated rats. Sumatriptan treatment blocked NAc dopamine release in IM‐treated rats receiving RVM lidocaine. Systemic sumatriptan did not alter pain relief‐induced CPP in rats with incisional injury. Interpretation Cephalic pain was unmasked in rats by assessment of motivated behavior to seek relief. Relief of pain activates the dopaminergic reward pathway to elicit negative reinforcement of behavior. Medications clinically effective for migraine headache selectively elicit relief of ongoing cephalic, but not postsurgical, noncephalic pain. These studies provide a platform for exploring migraine pathophysiology and for the discovery of new headache therapies. Ann Neurol 2013;74:257–265

ABSTRACTVenous thromboembolism (VTE) is a common, heritable disease resulting in high rates of hospitalization and mortality. Yet few associations between VTE and genetic variants, all in the coagulation pathway, have been established. To identify additional genetic determinants of VTE, we conducted a two‐stage genome‐wide association study (GWAS) among individuals of European ancestry in the extended cohorts for heart and aging research in genomic epidemiology (CHARGE) VTE consortium. The discovery GWAS comprised 1,618 incident VTE cases out of 44,499 participants from six community‐based studies. Genotypes for genome‐wide single‐nucleotide polymorphisms (SNPs) were imputed to approximately 2.5 million SNPs in HapMap and association with VTE assessed using study‐design appropriate regression methods. Meta‐analysis of these results identified two known loci, in F5 and ABO. Top 1,047 tag SNPs (P ≤ 0.0016) from the discovery GWAS were tested for association in an additional 3,231 cases and 3,536 controls from three case‐control studies. In the combined data from these two stages, additional genome‐wide significant associations were observed on 4q35 at F11 (top SNP rs4253399, intronic to F11) and on 4q28 at FGG (rs6536024, 9.7 kb from FGG; P < 5.0 × 10−13 for both). The associations at the FGG locus were not completely explained by previously reported variants. Loci at or near SUSD1 and OTUD7A showed borderline yet novel associations (P < 5.0 × 10−6) and constitute new candidate genes. In conclusion, this large GWAS replicated key genetic associations in F5 and ABO, and confirmed the importance of F11 and FGG loci for VTE. Future studies are warranted to better characterize the associations with F11 and FGG and to replicate the new candidate associations.

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) enhance insulin sensitivity and glucose homeostasis in rodent models of insulin resistance. These beneficial effects have been linked with anti-inflammatory properties, but emerging data suggest that the mechanisms may also converge on mitochondria. We evaluated the influence of dietary n-3 PUFAs on mitochondrial physiology and muscle lipid metabolites in the context of high-fat diet (HFD) in mice. Mice were fed control diets (10% fat), HFD (60% fat), or HFD with fish oil (HFD+FO, 3.4% kcal from n-3 PUFAs) for 10 wk. Body mass and fat mass increased similarly in HFD and HFD+FO, but n-3 PUFAs attenuated the glucose intolerance that developed with HFD and increased expression of genes that regulate glucose metabolism in skeletal muscle. Despite similar muscle triglyceride levels in HFD and HFD+FO, long-chain acyl-CoAs and ceramides were lower in the presence of fish oil. Mitochondrial abundance and oxidative capacity were similarly increased in HFD and HFD+FO compared with controls. Hydrogen peroxide production was similarly elevated in HFD and HFD+FO in isolated mitochondria but not in permeabilized muscle fibers, likely due to increased activity and expression of catalase. These results support a hypothesis that n-3 PUFAs protect glucose tolerance, in part by preventing the accumulation of bioactive lipid mediators that interfere with insulin action. Furthermore, the respiratory function of skeletal muscle mitochondria does not appear to be a major factor in sphingolipid accumulation, glucose intolerance, or the protective effects of n-3 PUFAs.

Objectives To investigate the incidence of carcinoma in situ ( CIS ) in Australia and examine implications for its diagnosis and management, as CIS of the urinary bladder is a non‐reportable disease in Australia. Methods Analysis of annual hospitalisation data using A ustralian I nstitute of H ealth and W elfare ( AIHW ) datasets showed an increase in CIS from 2001 onwards. To determine whether the increase seen with AIHW data represented a true increase in the rates offices, patient level data was examined using the Centre for Health record linkage ( CHeReL ) datasets. Results CHeReL linked data of 13 790 males and 5902 females, calculated the average incidence of CIS to be 20.9 per 100 000 and 6.5 per 100 000 respectively in those aged > 50 years, showing a rapid increase in the rates of CIS from 2001. There was an 11% ( P = 0.04) and 14% ( P = 0.02) annual increase in incidence of CIS in men and women and these rates increased with age. Conclusions National data ( AIHW ) substantially underestimate the incidence of CIS in the Australian population. Patient level data suggest CIS rates are rapidly increasing in Australia despite high treatment rates. Closer surveillance and awareness of these high rates warrants further study and we recommend that CIS be considered a reportable disease.

Abstract Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer's first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer's Association convened a research roundtable on the topic of NPS in AD. A major outcome of the roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The NPS‐PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome‐specific synthetic reviews and recommendations prepared by NPS‐PIA workgroups on depression, apathy, sleep, agitation, and psychosis.

Medical professionals and public consumers expect that new physical therapy graduates possess cognitive, technical, and behavioral skills required to provide safe and high‐quality care to patients. The purpose of this study was to determine if a repertoire of ten professional behaviors assessed at the beginning of doctorate of physical therapy education and before the first significant clinical internship could be enhanced in a semester course in gross human anatomy using individual formative feedback. During the human anatomy course, 28 first‐year physical therapy students completed six biweekly, anonymous self‐ and peer assessment surveys that targeted ten professional behaviors important to physical therapists. All professional behaviors were assessed using a five‐point Likert scale. Feedback reports occurred at week eight (mid‐semester) and week 16 (end‐of‐semester) and comprised the direct intervention components of this study. At the midpoint of the semester, professional behavior scores and narrative comments from weeks two, four, and six were compiled and shared with each student by one of three faculty members in a feedback session. Students then submitted biweekly self‐and peer professional behavior assessments (weeks 10, 12, and 14) for the remainder of the human anatomy course. Differences between preintervention and postintervention scores for each of the ten professional behaviors were compared using the Wilcoxon signed‐ranks test. Upon receiving mid‐semester individual feedback, students demonstrated significant improvement in each of the ten professional behaviors. Results from this study indicated a gross anatomy laboratory dissection experience during the first academic semester provided an effective opportunity for teaching and assessing professional behaviors of doctoral students in physical therapy. Anat Sci Educ 6: 324–331. © 2013 American Association of Anatomists.