Secondary prevention of osteoporosis in Australia: Analysis of government-dispensed prescription data

Background Osteoporosis is a common cause of disability and death in elderly men and women. Until 2007, Australian Government-subsidized use of oral bisphosphonates, raloxifene and calcitriol (1α,25-dihydroxycholecalciferol) was limited to secondary prevention (requiring x-ray evidence of previous low-trauma fracture). The cost to the Pharmaceutical Benefits Scheme was substantial (164 million Australian dollars in 2005/6). Objective To examine the dispensed prescriptions for oral bisphosphonates, raloxifene, calcitriol and two calcium products for the secondary prevention of osteoporosis (after previous low-trauma fracture) in the Australian population. Methods We analysed government data on prescriptions for oral bisphosphonates, raloxifene, calcitriol and two calcium products from 1995 to 2006, and by sex and age from 2002 to 2006. Prescription counts were converted to defined daily doses (DDD)/1000 population/day. This standardized drug utilization method used census population data, and adjusts for the effects of aging in the Australian population. Results Total bisphosphonate use increased 460% from 2.19 to 12.26 DDD/1000 population/day between June 2000 and June 2006. The proportion of total bisphosphonate use in June 2006 was 75.1% alendronate, 24.6% risedronate and 0.3% etidronate. Raloxifene use in June 2006 was 1.32 DDD/1000 population/day. The weekly forms of alendronate and risedronate, introduced in 2001 and 2003, respectively, were quickly adopted. Bisphosphonate use peaked at age 80–89 years in females and 85–94 years in males, with 3-fold higher use in females than in males. Conclusions Pharmaceutical intervention for osteoporosis in Australia is increasing with most use in the elderly, the population at greatest risk of fracture. However, fracture prevalence in this population is considerably higher than prescribing of effective anti-osteoporosis medications, representing a missed opportunity for the quality use of medicines.

The complete genome sequence of Escherichia coli EC958: a high quality reference sequence for the globally disseminated multidrug resistant E. coli O25b:H4-ST131 clone

Escherichia coli ST131 is now recognised as a leading contributor to urinary tract and bloodstream infections in both community and clinical settings. Here we present the complete, annotated genome of E. coli EC958, which was isolated from the urine of a patient presenting with a urinary tract infection in the Northwest region of England and represents the most well characterised ST131 strain. Sequencing was carried out using the Pacific Biosciences platform, which provided sufficient depth and read-length to produce a complete genome without the need for other technologies. The discovery of spurious contigs within the assembly that correspond to site-specific inversions in the tail fibre regions of prophages demonstrates the potential for this technology to reveal dynamic evolutionary mechanisms. E. coli EC958 belongs to the major subgroup of ST131 strains that produce the CTX-M-15 extended spectrum β-lactamase, are fluoroquinolone resistant and encode the fimH30 type 1 fimbrial adhesin. This subgroup includes the Indian strain NA114 and the North American strain JJ1886. A comparison of the genomes of EC958, JJ1886 and NA114 revealed that differences in the arrangement of genomic islands, prophages and other repetitive elements in the NA114 genome are not biologically relevant and are due to misassembly. The availability of a high quality uropathogenic E. coli ST131 genome provides a reference for understanding this multidrug resistant pathogen and will facilitate novel functional, comparative and clinical studies of the E. coli ST131 clonal lineage.

Creating quality cross-media experiences

There are many ways to create a cross-media project, but there are approaches which facilitate a quality implementation. The crucial starting point with any creative project is a great story or game. However, because the cross-media artform is still emerging and many practitioners are new to the area, just how to produce a quality cross-media project is not well known. Based on my work on both small- and large-scale projects, I outline ten approaches that will aid in facilitating a quality cross-media project.

Synthesis and toxicological evaluation of a chitosan‑L‑leucine conjugate for pulmonary drug delivery applications

Herein are reported the synthesis of a conjugate of chitosan with L-leucine, the preparation of nanoparticles from both chitosan and the conjugate for use in pulmonary drug delivery, and the in vitro evaluation of toxicity and inflammatory effects of both the polymers and their nanoparticles on the bronchial epithelial cell line, BEAS-2B. The nanoparticles, successfully prepared both from chitosan and the conjugate, had a diameter in the range of 10−30 nm. The polymers and their nanoparticles were tested for their effects on cell viability by MTT assay, on trans-epithelial permeability by using sodium fluorescein as a fluid phase marker, and on IL-8 secretion by ELISA. The conjugate nanoparticles had a low overall toxicity (IC50 = 2 mg/mL following 48 h exposure; no induction of IL-8 release at 0.5 mg/mL concentration), suggesting that they may be safe for pulmonary drug delivery applications.

Evidence of associations between cytokine gene polymorphisms and quality of life in patients with cancer and their family caregivers

PURPOSE/OBJECTIVES: To identify latent classes of individuals with distinct quality-of-life (QOL) trajectories, to evaluate for differences in demographic characteristics between the latent classes, and to evaluate for variations in pro- and anti-inflammatory cytokine genes between the latent classes. DESIGN: Descriptive, longitudinal study. SETTING: Two radiation therapy departments located in a comprehensive cancer center and a community-based oncology program in northern California. SAMPLE: 168 outpatients with prostate, breast, brain, or lung cancer and 85 of their family caregivers (FCs). METHODS: Growth mixture modeling (GMM) was employed to identify latent classes of individuals based on QOL scores measured prior to, during, and for four months following completion of radiation therapy. Single nucleotide polymorphisms (SNPs) and haplotypes in 16 candidate cytokine genes were tested between the latent classes. Logistic regression was used to evaluate the relationships among genotypic and phenotypic characteristics and QOL GMM group membership. MAIN RESEARCH VARIABLES: QOL latent class membership and variations in cytokine genes. FINDINGS: Two latent QOL classes were found: higher and lower. Patients and FCs who were younger, identified with an ethnic minority group, had poorer functional status, or had children living at home were more likely to belong to the lower QOL class. After controlling for significant covariates, between-group differences were found in SNPs in interleukin 1 receptor 2 (IL1R2) and nuclear factor kappa beta 2 (NFKB2). For IL1R2, carrying one or two doses of the rare C allele was associated with decreased odds of belonging to the lower QOL class. For NFKB2, carriers with two doses of the rare G allele were more likely to belong to the lower QOL class. CONCLUSIONS: Unique genetic markers in cytokine genes may partially explain interindividual variability in QOL. IMPLICATIONS FOR NURSING: Determination of high-risk characteristics and unique genetic markers would allow for earlier identification of patients with cancer and FCs at higher risk for poorer QOL. Knowledge of these risk factors could assist in the development of more targeted clinical or supportive care interventions for those identified.

Colloidal drug probe : Method development and validation for adhesion force measurement using Atomic Force Microscopy

This study demonstrates a novel technique of preparing drug colloid probes to determine the adhesion force between a model drug salbutamol sulphate (SS) and the surfaces of polymer microparticles to be used as carriers for the dispersion of drug particles from dry powder inhaler (DPI) formulations. Model silica probes of approximately 4 lm size, similar to a drug particle used in DPI formulations, were coated with a saturated SS solution with the aid of capillary forces acting between the silica probe and the drug solution. The developed method of ensuring a smooth and uniform layer of SS on the silica probe was validated using X-ray Photoelectron Spectroscopy (XPS) and Scanning Electron Microscopy (SEM). Using the same technique, silica microspheres pre-attached on the AFM cantilever were coated with SS. The adhesion forces between the silica probe and drug coated silica (drug probe) and polymer surfaces (hydrophilic and hydrophobic) were determined. Our experimental results showed that the technique for preparing the drug probe was robust and can be used to determine the adhesion force between hydrophilic/ hydrophobic drug probe and carrier surfaces to gain a better understanding on drug carrier adhesion forces in DPI formulations.

Intravenous injection of leconotide, an omega conotoxin : synergistic antihyperalgesic effects with morphine in a rat model of bone cancer pain

Objective.  Leconotide (CVID, AM336, CNSB004) is an omega conopeptide similar to ziconotide, which blocks voltage sensitive calcium channels. However, unlike ziconotide, which must be administered intrathecally, leconotide can be given intravenously because it is less toxic. This study investigated the antihyperalgesic potency of leconotide given intravenously alone and in combinations with morphine-administered intraperitoneally, in a rat model of bone cancer pain. Design.  Syngeneic rat prostate cancer cells AT3B-1 were injected into one tibia of male Wistar rats. The tumor expanded within the bone causing hyperalgesia to heat applied to the ipsilateral hind paw. Measurements were made of the maximum dose (MD) of morphine and leconotide given alone and in combinations that caused no effect in an open-field activity monitor, rotarod, and blood pressure and heart rate measurements. Paw withdrawal thresholds from noxious heat were measured. Dose response curves for morphine (0.312–5.0 mg/kg intraperitoneal) and leconotide (0.002–200 µg/kg intravenous) given alone were plotted and responses compared with those caused by morphine and leconotide in combinations. Results.  Leconotide caused minimal antihyperalgesic effects when administered alone. Morphine given alone intraperitoneally caused dose-related antihyperalgesic effects (ED50 = 2.40 ± 1.24 mg/kg), which were increased by coadministration of leconotide 20 µg/kg (morphine ED50 = 0.16 ± 1.30 mg/kg); 0.2 µg/kg (morphine ED50 = 0.39 ± 1.27 mg/kg); and 0.02 µg/kg (morphine ED50 = 1.24 ± 1.30 mg/kg). Conclusions.  Leconotide caused a significant increase in reversal by morphine of the bone cancer-induced hyperalgesia without increasing the side effect profile of either drug. Clinical Implication.  Translation into clinical practice of the method of analgesia described here will improve the quantity and quality of analgesia in patients with bone metastases. The use of an ordinary parenteral route for administration of the calcium channel blocker (leconotide) at low dose opens up the technique to large numbers of patients who could not have an intrathecal catheter for drug administration. Furthermore, the potentiating synergistic effect with morphine on hyperalgesia without increased side effects will lead to greater analgesia with improved quality of life.

The impact of cataract surgery on vision-related quality of life for bilateral cataract patients in Ho Chi Minh City, Vietnam : a prospective study

Background To determine the impact of cataract surgery on vision-related quality of life (VRQOL) and examine the association between objective visual measures and change in VRQOL after surgery among bilateral cataract patients in Ho Chi Minh City, Vietnam. Methods A cohort of older patients with bilateral cataract was assessed one week before and one to three months after first eye or both eye cataract surgery. Visual measures including visual acuity, contrast sensitivity and stereopsis were obtained. Vision-related quality of life was assessed using the NEI VFQ-25. Descriptive analyses and a generalized linear estimating equation (GEE) analysis were undertaken to measure change in VRQOL after surgery. Results Four hundred and thirteen patients were assessed before cataract surgery and 247 completed the follow-up assessment one to three months after first or both eye cataract surgery. Overall, VRQOL significantly improved after cataract surgery (p < 0.001) particularly after both eye surgeries. Binocular contrast sensitivity (p < 0.001) and stereopsis (p < 0.001) were also associated with change in VRQOL after cataract surgery. Visual acuity was not associated with VRQOL. Conclusions Cataract surgery significantly improved VRQOL among bilateral cataract patients in Vietnam. Contrast sensitivity as well as stereopsis, rather than visual acuity significantly affected VRQOL after cataract surgery.

2nd ESMO Consensus Conference on Lung Cancer : non-small-cell lung cancer first-line/second and further lines in advanced disease

To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on 1st line / 2nd and further lines of treatment in advanced disease. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Health Information Exchange in the wake of ‘big data’ paradigm – the theme is from ‘quality of information to quality of life’

Health Information Exchange (HIE) is an interesting phenomenon. It is a patient centric health and/or medical information management scenario enhanced by integration of Information and Communication Technologies (ICT). While health information systems are repositioning complex system directives, in the wake of the ‘big data’ paradigm, extracting quality information is challenging. It is anticipated that in this talk, ICT enabled healthcare scenarios with big data analytics will be shared. In addition, research and development regarding big data analytics, such as current trends of using these technologies for health care services and critical research challenges when extracting quality of information to improve quality of life will be discussed.

Profiling high-range speeding offenders : investigating criminal history, personal characteristics, traffic offences, and crash history

This paper reports profiling information for speeding offenders and is part of a larger project that assessed the deterrent effects of increased speeding penalties in Queensland, Australia, using a total of 84,456 speeding offences. The speeding offenders were classified into three groups based on the extent and severity of an index offence: once-only low-rang offenders; repeat high-range offenders; and other offenders. The three groups were then compared in terms of personal characteristics, traffic offences, crash history and criminal history. Results revealed a number of significant differences between repeat high-range offenders and those in the other two offender groups. Repeat high-range speeding offenders were more likely to be male, younger, hold a provisional and a motorcycle licence, to have committed a range of previous traffic offences, to have a significantly greater likelihood of crash involvement, and to have been involved in multiple-vehicle crashes than drivers in the other two offender types. Additionally, when a subset of offenders’ criminal histories were examined, results revealed that repeat high-range speeding offenders were also more likely to have committed a previous criminal offence compared to once only low-range and other offenders and that 55.2% of the repeat high-range offenders had a criminal history. They were also significantly more likely to have committed drug offences and offences against order than the once only low-range speeding offenders, and significantly more likely to have committed regulation offences than those in the other offenders group. Overall, the results indicate that speeding offenders are not an homogeneous group and that, therefore, more tailored and innovative sanctions should be considered and evaluated for high-range recidivist speeders because they are a high-risk road user group.