Role of DOTATATE-PET/CT in preoperative assessment of phaeochromocytoma and paragangliomas.

CONTEXT: Diagnosis of paragangliomas (PGL) and phaeochromocytomas (PC) can be challenging particularly if the tumour is small. Detection of metastatic disease is important for comprehensive management of malignant PC/PGL. Somatostatin receptor imaging (SRI) agents have high sensitivity for these tumours, particularly the DOTA family of radiopharmaceuticals labelled with 68 Gallium. OBJECTIVE: To describe the utility of SRI in primary assessment (ie before surgery) for PC/PGL and whether measures of maximum standardized uptake (SUVmax) could be used to distinguish between adrenal adenomas and PCs. DESIGN: Retrospective analysis of patients with PC and PGL between 2012 and 2017. PATIENTS: Somatostatin receptor imaging (SRI) was performed for suspected PC (n = 46) or PGL (n = 27) of which 36 were during primary assessment and 37 during secondary assessment (follow-up after surgery). For comparison of adrenal SUVmax, scans from 30 patients without suspected PC/PGL (20 with normal adrenals; 10 with incidental adenomas) were evaluated. MEASUREMENTS: Baseline description, sensitivity, specificity, Youden's index. RESULTS: Sensitivity of DOTATATE-PET was 88% for PC and 100% for PGL. False-negative scans were seen in 2/10 PCs < 28 mm and in 1/14 PCs > 28 mm which had features of cystic degeneration. SUVmax of PCs and PGLs was more than double compared to adrenal adenomas (P > .001). CONCLUSION: Somatostatin receptor imaging (SRI) has high sensitivity in primary assessment for PC and PGL. We recommend that SRI should be performed as part of primary assessment in all suspected PGLs (due to higher risk of multifocal lesions) and in PCs suspected to be associated with hereditary syndromes or metastases.

Physician Dispensing of Oxycodone and Other Commonly Used Opioids, 2000-2015, United States.

Objective: An average of 91 people in the United States die every day from an opioid-related overdose (including prescription opioids and heroin). The direct dispensing of opioids from health care practitioner offices has been linked to opioid-related harms. The objective of this study is to describe the changing nature of the volume of this type of prescribing at the state level. Methods: This descriptive study examines the distribution of opioids by practitioners using 1999-2015 Automation of Reports and Consolidated Orders System data. Analyses were restricted to opioids distributed to practitioners. Amount distributed (morphine milligram equivalents [MMEs]) and number of practitioners are presented. Results: Patterns of distribution to practitioners and the number of practitioners varied markedly by state and changed dramatically over time. Comparing 1999 with 2015, the MME distributed to dispensing practitioners decreased in 16 states and increased in 35. Most notable was the change in Florida, which saw a peak of 8.94 MMEs per 100,000 persons in 2010 (the highest distribution in all states in all years) and a low of 0.08 in 2013. Discussion: This study presents the first state estimates of office-based dispensing of opioids. Increases in direct dispensing in recent years may indicate a need to monitor this practice and consider whether changes are needed. Using controlled substances data to identify high prescribers and dispensers of opioids, as well as examining overall state trends, is a foundational activity to informing the response to potentially high-risk clinical practices.

Sleep-Related Infant Deaths in Victoria: A Retrospective Case Series Study.

BACKGROUND: There is general agreement that in some circumstances, sharing a sleep surface of any kind with an infant increases the risk of sudden unexpected death in infancy. There is a paucity of research conducted in Australia examining this issue. This study examines the frequency and distribution of sleep-related infant deaths in a defined population, and reports the proportion that occurred in the context of bed-sharing. METHODS: A retrospective population-based case series study was conducted of infants (≤365 days) who died in a sleeping context during the period 1 January 2008 to 31 December 2010 in the state of Victoria, Australia. Information about the infant, caregiver, sleeping environment and bed-sharing was collected from a review of the coroner's death investigation record. RESULTS: During the 3-year study period, 72 infant deaths occurred in a sleeping context. Of these, 33 (45.8 %) occurred in the context of bed-sharing: n = 7 in 2008; n = 11 in 2009; and n = 15 in 2010. Further analysis of the 33 deaths occurring in the context of bed-sharing showed that in this group, bed-sharing was largely intentional, habitual and most often involved the mother as one of the parties. CONCLUSIONS: Given the case series nature of the study design, a causal relationship between bed-sharing and infant death could not be inferred. However the fact that nearly half of all sleep-related deaths occurred in the context of bed-sharing, provides strong support for the need to undertake definitive analytic studies in Australia so that evidence-based advice can be provided to families regarding the safety of bed-sharing practices.

Building a multisystemic understanding of societal resilience to the COVID-19 pandemic.

The current global systemic crisis reveals how globalised societies are unprepared to face a pandemic. Beyond the dramatic loss of human life, the COVID-19 pandemic has triggered widespread disturbances in health, social, economic, environmental and governance systems in many countries across the world. Resilience describes the capacities of natural and human systems to prevent, react to and recover from shocks. Societal resilience to the current COVID-19 pandemic relates to the ability of societies in maintaining their core functions while minimising the impact of the pandemic and other societal effects. Drawing on the emerging evidence about resilience in health, social, economic, environmental and governance systems, this paper delineates a multisystemic understanding of societal resilience to COVID-19. Such an understanding provides the foundation for an integrated approach to build societal resilience to current and future pandemics.

Rethinking conceptual frameworks and models of health and natural environments.

This article considers conceptual frameworks and models applied in research about the multiple relations between human contact with natural environments (specifically green public spaces), diverse kinds of human activities and uses of those spaces, and effects on physical and mental health. Conceptual frameworks are tools for thinking about such complex subjects. Conceptual models represent the multiple relations between key factors and variables. These models can be used to represent the mutual interactions between the core components of environmental conditions of specific green public spaces, the main kinds of human activities in those settings, and various impacts on health. A literature search showed that the authors of various conceptual models used a metaphor of pathways to represent relations between explanatory variables by linear cause-effect relations. Mutual interaction between key variables and feedback loops between different components of the model are rarely included. Hence, it is argued that these models do not represent the complexity of real world situations. The authors propose a systemic conceptual framework founded on core principles of human ecology. The proposed conceptual framework and model have been formulated during and after an EU 7th Framework project about the ''Positive Health Effects of the Natural Outdoor Environment in Typical Populations in Different Regions of Europe."

Healthy aging as an intervention to minimize injury from falls among older people.

With global trends toward population aging, many countries are adopting healthy aging policies to minimize disability and increase quality in the extended years of life. Falls in older people are a major contributor to functional decline generally associated with aging. Based on a study quantifying the relationship between healthy aging factors and risk of fall-related hip fracture in community-dwelling older people, this paper discusses evidence for the promotion of healthy aging as a population-based intervention for prevention of injuries from falls. To examine the protective effect of healthy aging on the risk of fall-related hip fractures, a case-control study was conducted with 387 participants. Persons aged 65 and over hospitalized with a fall-related hip fracture were matched with community-based controls recruited via electoral roll sampling. A questionnaire designed to assess lifestyle risk factors, identified as determinants of healthy aging, was administered during face-to-face interviews. After adjustment for health status and demographic factors, a number of lifestyle factors were seen to have a significant independent protective effect on the risk of hip fracture. These included never smoking, moderate alcohol consumption, being active, maintaining normal weight, and being proactive in preventive health care. Psychosocial factors included having supportive environments and personal resources to cope with stress. This study identified a range of modifiable lifestyle factors associated with fall-related hip fracture, suggesting that the "healthy aging" paradigm offers a comprehensive approach to falls injury prevention, and thus supports the adoption of healthy aging policies to extend years of quality life among older persons.

Annexin 1 and the biology of the neutrophil.

This overview will focus on one aspect of neutrophil biology, which is the selective activation of the annexin 1 system in relation to the process of cell extravasation. Besides the current view about the biochemistry of annexin 1 and annexin 1 receptor(s) up-regulation within the microenvironment of the adherent neutrophils, we will also comment on the final result achieved by activation of the system, which is inhibition of neutrophil recruitment. In view of the historical link between annexin 1 and glucocorticoids, the potential for the annexin 1 system in mediating at least some of the anti-inflammatory actions of these powerful drugs is also discussed.

Sources of coding discrepancies in injury morbidity data: implications for injury surveillance.

The aim of this study is to examine the sources of coding discrepancy for injury morbidity data and explore the implications of these sources for injury surveillance. An on-site medical record review and recoding study was conducted for 4373 injury-related hospital admissions across Australia. Codes from the original dataset were compared with the recoded data to explore the reliability of coded data and sources of discrepancy. The most common reason for differences in coding overall was assigning the case to a different external cause category with 9.5% assigned to a different category. Differences in the specificity of codes assigned within a category accounted for 7.8% of coder difference. Differences in intent assignment accounted for 3.7% of the differences in code assignment. In the situation where 8% of cases are misclassified by major category, the setting of injury targets on the basis of extent of burden is a somewhat blunt instrument. Monitoring the effect of prevention programs aimed at reducing risk factors is not possible in datasets with this level of misclassification error in injury cause subcategories. Future research is needed to build the evidence base around the quality and utility of the International Statistical Classification of Diseases and Related Health Problems (ICD) classification system and the application of use of this for injury surveillance in the hospital environment.

Identification of alcohol involvement in injury-related hospitalisations using routine data compared to medical record review.

OBJECTIVE: To quantify the extent that alcohol related injuries are adequately identified in hospitalisation data using ICD-10-AM codes indicative of alcohol involvement. METHOD: A random sample of 4,373 injury-related hospital separations from 1 July 2002 to 30 June 2004 were obtained from a stratified random sample of 50 hospitals across four states in Australia. From this sample, cases were identified as involving alcohol if they contained an ICD-10-AM diagnosis or external cause code referring to alcohol, or if the text description extracted from the medical records mentioned alcohol involvement. RESULTS: Overall, identification of alcohol involvement using ICD codes detected 38% of the alcohol-related sample, while almost 94% of alcohol-related cases were identified through a search of the text extracted from the medical records. The resultant estimate of alcohol involvement in injury-related hospitalisations in this sample was 10%. Emergency department records were the most likely to identify whether the injury was alcohol-related with almost three-quarters of alcohol-related cases mentioning alcohol in the text abstracted from these records. CONCLUSIONS AND IMPLICATIONS: The current best estimates of the frequency of hospital admissions where alcohol is involved prior to the injury underestimate the burden by around 62%. This is a substantial underestimate that has major implications for public policy, and highlights the need for further work on improving the quality and completeness of routine administrative data sources for identification of alcohol-related injuries.

The use of narrative text for injury surveillance research: a systematic review.

OBJECTIVE: To summarise the extent to which narrative text fields in administrative health data are used to gather information about the event resulting in presentation to a health care provider for treatment of an injury, and to highlight best practise approaches to conducting narrative text interrogation for injury surveillance purposes. DESIGN: Systematic review. DATA SOURCES: Electronic databases searched included CINAHL, Google Scholar, Medline, Proquest, PubMed and PubMed Central. Snowballing strategies were employed by searching the bibliographies of retrieved references to identify relevant associated articles. SELECTION CRITERIA: Papers were selected if the study used a health-related database and if the study objectives were to a) use text field to identify injury cases or use text fields to extract additional information on injury circumstances not available from coded data or b) use text fields to assess accuracy of coded data fields for injury-related cases or c) describe methods/approaches for extracting injury information from text fields. METHODS: The papers identified through the search were independently screened by two authors for inclusion, resulting in 41 papers selected for review. Due to heterogeneity between studies meta-analysis was not performed. RESULTS: The majority of papers reviewed focused on describing injury epidemiology trends using coded data and text fields to supplement coded data (28 papers), with these studies demonstrating the value of text data for providing more specific information beyond what had been coded to enable case selection or provide circumstantial information. Caveats were expressed in terms of the consistency and completeness of recording of text information resulting in underestimates when using these data. Four coding validation papers were reviewed with these studies showing the utility of text data for validating and checking the accuracy of coded data. Seven studies (9 papers) described methods for interrogating injury text fields for systematic extraction of information, with a combination of manual and semi-automated methods used to refine and develop algorithms for extraction and classification of coded data from text. Quality assurance approaches to assessing the robustness of the methods for extracting text data was only discussed in 8 of the epidemiology papers, and 1 of the coding validation papers. All of the text interrogation methodology papers described systematic approaches to ensuring the quality of the approach. CONCLUSIONS: Manual review and coding approaches, text search methods, and statistical tools have been utilised to extract data from narrative text and translate it into useable, detailed injury event information. These techniques can and have been applied to administrative datasets to identify specific injury types and add value to previously coded injury datasets. Only a few studies thoroughly described the methods which were used for text mining and less than half of the studies which were reviewed used/described quality assurance methods for ensuring the robustness of the approach. New techniques utilising semi-automated computerised approaches and Bayesian/clustering statistical methods offer the potential to further develop and standardise the analysis of narrative text for injury surveillance.

Special issues in injury prevention research: developing the science of program implementation.

INTRODUCTION: Despite widespread application of the public health approach to injury prevention, there is an acknowledged limitation in the extent to which it facilitates translation of research evidence to injury prevention practice. AIM: In this paper we clarify the ecoepidemiological principles that underpin the public health approach to injury control in order to support explicit efforts to address the multilevel component causes and improve the evidence base on which effective program implementation depends. KEYPOINTS: If injury causation is understood in terms of the ecoepidemiological model rather than the proximal risk factor model, then quantification of the context in which the event occurs is evidently as important as quantification of the energy exchange event itself. The ecoepidemiological model of injury causation recognises barriers and facilitators to injury prevention as component causes of population burden of injury and thus delineates these factors as legitimate targets for intervention. Injury prevention programs that are designed to specifically address the factors causally related to the program's implementation, as well as the contextual factors that determine the characteristics of the energy exchange event, are more likely to be implemented and more likely to result in effective uptake of recommended energy exchange countermeasures. CONCLUSION: Interventions to reduce the burden of injury in the population should address the individual level factors that increase the risk of injury, but also the upstream factors that influence the extent to which there is widespread adoption by individuals of the recommended countermeasures.

The reliability of information on work-related injuries available from hospitalisation data in Australia.

OBJECTIVE: To examine the reliability of work-related activity coding for injury-related hospitalisations in Australia. METHOD: A random sample of 4,373 injury-related hospital separations from 1 July 2002 to 30 June 2004 were obtained from a stratified random sample of 50 hospitals across four states in Australia. From this sample, cases were identified as work-related if they contained an ICD-10-AM work-related activity code (U73) allocated by either: (i) the original coder; (ii) an independent auditor, blinded to the original code; or (iii) a research assistant, blinded to both the original and auditor codes, who reviewed narrative text extracted from the medical record. The concordance of activity coding and number of cases identified as work-related using each method were compared. RESULTS: Of the 4,373 cases sampled, 318 cases were identified as being work-related using any of the three methods for identification. The original coder identified 217 and the auditor identified 266 work-related cases (68.2% and 83.6% of the total cases identified, respectively). Around 10% of cases were only identified through the text description review. The original coder and auditor agreed on the assignment of work-relatedness for 68.9% of cases. CONCLUSIONS AND IMPLICATIONS: The best estimates of the frequency of hospital admissions for occupational injury underestimate the burden by around 32%. This is a substantial underestimate that has major implications for public policy, and highlights the need for further work on improving the quality and completeness of routine, administrative data sources for a more complete identification of work-related injuries.

Discovery of novel hydantoins as selective non-hydroxamate inhibitors of tumor necrosis factor-alpha converting enzyme (TACE).

A series of novel hydantoins was designed and synthesized as structural alternatives to hydroxamate inhibitors of TACE. 5-Mono- and di-substituted hydantoins exhibited activity with IC50 values of 11-60 nM against porcine TACE in vitro and excellent selectivity against other MMPs.

Role of annexin 1 gene expression in mouse craniofacial bone development.

BACKGROUND: Annexin 1 is a 37-kDa protein that has complex intra- and extracellular effects. To discover whether the absence of this protein alters bone development, we monitored this event in the annexin-A1 null mice in comparison with littermate wild-type controls. METHODS: Radiographic and densitometry methods were used for the assessment of bone in annexin-A1 null mice at a gross level. We used whole-skeleton staining, histological analysis, and Western blotting techniques to monitor changes at the tissue and cellular levels. RESULTS: There were no gross differences in the appendicular skeleton between the genotypes, but an anomalous development of the skull was observed in the annexin-A1 null mice. This was characterized in the newborn annexin-A1 null animals by a delayed intramembranous ossification of the skull, incomplete fusion of the interfrontal suture and palatine bone, and the presence of an abnormal suture structure. The annexin-A1 gene was shown to be active in osteocytes during this phase and COX-2 was abundantly expressed in cartilage and bone taken from annexin-A1 null mice. CONCLUSIONS: Expression of the annexin-A1 gene is important for the normal development of the skull in mice, possibly through the regulation of osteoblast differentiation and a secondary effect on the expression of components of the cPLA2-COX-2 system.

Health-protective behaviours and risk of fall-related hip fractures: a population-based case-control study.

BACKGROUND: Fall-related hip fractures are one of the most common causes of disability and mortality in older age. The study aimed to quantify the relationship between lifestyle behaviours and the risk of fall-related hip fracture in community-dwelling older people. The purpose was to contribute evidence for the promotion of healthy ageing as a population-based intervention for falls injury prevention. METHODS: A case-control study was conducted with 387 participants, with a case-control ratio of 1:2. Incident cases of fall-related hip fracture in people aged 65 and over were recruited from six hospital sites in Brisbane, Australia, in 2003-04. Community-based controls, matched by age, sex and postcode, were recruited via electoral roll sampling. A questionnaire designed to assess lifestyle risk factors, identified as determinants of healthy ageing, was administered at face-to-face interviews. RESULTS: Behavioural factors which had a significant independent protective effect on the risk of hip fracture included never smoking [adjusted odds ratio (AOR): 0.33 (0.12-0.88)], moderate alcohol consumption in mid- and older age [AOR: 0.49 (0.25-0.95)], not losing weight between mid- and older age [AOR: 0.36 (0.20-0.65)], playing sport in older age [AOR: 0.49 (0.29-0.83)] and practising a greater number of preventive medical care [AOR: 0.54 (0.32-0.94)] and self-health behaviours [AOR: 0.56 (0.33-0.94)]. CONCLUSION: With universal exposures, clear associations and modifiable behavioural factors, this study has contributed evidence to reduce the major public health burden of fall-related hip fractures using readily implemented population-based healthy ageing strategies.

N-Arylalkylpiperidine urea derivatives as CC chemokine receptor-3 (CCR3) antagonists.

The synthesis and structure-activity relationships of N-arylalkylpiperidylmethyl ureas as antagonists of the CC chemokine receptor-3 (CCR3) are presented. These compounds displayed potent binding to the receptor as well as functional antagonism of eotaxin-elicited effects on eosinophils.

Asymmetric synthesis of trans-2,3-piperidinedicarboxylic acid and trans-3,4-piperidinedicarboxylic acid derivatives.

Asymmetric syntheses of (2S,3S)-3-(tert-butoxycarbonyl)-2-piperidinecarboxylic acid (1b), (3R,4S)-4-(tert-butoxycarbonyl)-3-piperidinecarboxylic acid (2b), and their corresponding N-Boc and N-Cbz protected analogues 8a,b and 17a,b are described. Enantiomerically pure 1b has been synthesized in five steps starting from L-aspartic acid beta-tert-butyl ester. Tribenzylation of the starting material followed by alkylation with allyl iodide using KHMDS produces the key intermediate 5a in a 6:1 diastereomeric excess. Upon hydroboration, the alcohol 6a is oxidized, and the resulting aldehyde 7 is subjected to a ring closure via reductive amination, providing 1b in an overall yield of 38%. Optically pure 2b has been synthesized beginning with N-Cbz-beta-alanine. The synthesis involves the induction of the first stereogenic center using Evans's chemistry and sequential LDA-promoted alkylations with tert-butyl bromoacetate and allyl iodide. Further elaboration by ozonolysis and reductive amination affords 2b in an overall yield of 28%.

Modelling trends in woody vegetation structure in semi-arid Australia as determined from aerial photography.

Accounting of carbon stocks in woody vegetation for greenhouse purposes requires definition of medium term trends with accurate error assessment. Tree and shrub cover was sampled through time at randomly located sites over a large area of central Queensland, Australia using aerial photography from 1945 to 1999. Calibration models developed from field data for the same land types as those represented within the study area allowed for the extrapolation of overstorey and understorey cover, basal area and biomass values and these were modelled as trends over the latter half of the 20th century. These structural attributes have declined over the region because of land clearing with values for biomass changing from a mean of 58.0(+/-1.2)t/ha in 1953 to 41.1(+/-1.0)t/ha in 1991. The biomass of Acacia on clay and Eucalypt on texture contrast soils land types has declined most dramatically. Within uncleared vegetation there was an overall trend of increase from 56.1(+/-1.2)t/ha in 1951 to 67.6(+/-1.3)t/ha in 1995. The increase in structural attributes within uncleared vegetation was most pronounced for the Eucalypt on texture contrast soils and Eucalypt on clay land types. It was demonstrated that the sites sampled were representative of their land types and that spatial bias of the photography, undetected tree-killing, sampling error, inherent variability of structural attributes and measurement error should not have impacted greatly on bias or precision of trend estimates for well-sampled land types. Certainly the errors are not likely to be substantial for trends averaged over all land types and they provide an accurate assessment of the magnitude and direction of change. The technique presented here would appear to be a robust means of accounting for the above-ground woody component of woodlands and open forests and will also contribute to a broader understanding of savanna dynamics.

Rational design, synthesis and structure-activity relationships of a cyclic succinate series of TNF-alpha converting enzyme inhibitors. Part 1: lead identification.

Rational design based on the broad spectrum MMP inhibitor CGS 27023A led to the identification of a novel series of cyclic succinate TACE inhibitors. As a mixture of two enantiomers, the lead compound 17b exhibited potent enzyme activity (IC(50)=8 nM) in the inhibition of porcine TNF-alpha converting enzyme (pTACE) and excellent selectivity over aggrecanase and MMP-1, -2 and -9.