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.

Twitter-archive und die Herausforderungen von "Big Social Data" für die Medien- und Kommunikationswissenschaft

Twitter ist eine besonders nützliche Quelle für Social-Media-Daten: mit dem Twitter-API (dem Application Programming Interface, das einen strukturierten Zugang zu Kommunikationsdaten in standardisierten Formaten bietet) ist es Forschern möglich, mit ein wenig Mühe und ausreichenden technische Ressourcen sehr große Archive öffentlich verbreiteter Tweets zu bestimmten Themen, Interessenbereichen, oder Veranstaltungen aufzubauen. Grundsätzlich liefert das API sehr langen Listen von Hunderten, Tausenden oder Millionen von Tweets und den Metadaten zu diesen Tweets; diese Daten können dann auf verschiedentlichste Weise extrahiert, kombiniert, und visualisiert werden, um die Dynamik der Social-Media-Kommunikation zu verstehen. Diese Forschung ist häufig um althergebrachte Fragestellungen herum aufgebaut, wird aber in der Regel in einem bislang unbekannt großen Maßstab durchgeführt. Die Projekte von Medien- und Kommunikationswissenschaftlern wie Papacharissi und de Fatima Oliveira (2012), Wood und Baughman (2012) oder Lotan et al. (2011) – um nur eine Handvoll der letzten Beispiele zu nennen – sind grundlegend auf Twitterdatensätze aufgebaut, die jetzt routinemäßig Millionen von Tweets und zugehörigen Metadaten umfassen, erfaßt nach einer Vielzahl von Kriterien. Was allen diesen Fällen gemein ist, ist jedoch die Notwendigkeit, neue methodische Wege in der Verarbeitung und Analyse derart großer Datensätze zur medienvermittelten sozialen Interaktion zu gehen.

Nephrotoxicity and nephrocarcinogenicity of dinitrotoluene : new aspects to be considered

Technical dinitrotoluene (DNT) is a mixture of 2,4- and 2,6-DNT. In humans, industrial or environmental exposure can occur orally, by inhalation, or by skin contact. The classification of DNT as an 'animal carcinogen' is based on the formation of malignant tumors in kidneys, liver, and mammary glands of rats and mice. Clear signs of toxic nephropathy were found in rats dosed with DNT, and the concept was derived of an interrelation between renal toxicity and carcinogenicity. Recent data point to the carcinogenicity of DNT on the urinary tract of exposed humans. Between 1984 and 1997, 6 cases of urothelial cancer and 14 cases of renal cell cancer were diagnosed in a group of 500 underground mining workers in the copper mining industry of the former GDR and having high exposures to explosives containing technical DNT. The incidences of both urothelial and renal cell tumors in this group were 4.5 and 14.3 times higher, respectively, than anticipated on the basis of the cancer registers of the GDR. The genotyping of all identified tumor patients for the polymorphic enzymes NAT2, GSTM1, and GSTT1 identified the urothelial tumor cases as exclusively 'slow acetylates'. A group of 161 miners highly exposed to DNT was investigated for signs of subclinical renal damage. The exposures were categorized semi-quantitatively into 'low', 'medium', 'high', and 'very high'. A straight dose-dependence of the excretion of urinary biomarker proteins with the ranking of exposure was seen. Biomarker excretion (alpha1-microglobulin, glutathione S-transferases alpha and pi) indicated that DNT-induced damage was directed toward the tubular system. New data on DNT-exposed humans appear consistent with the concept of cancer initiation by DNT isomers and the subsequent promotion of renal carcinogenesis by selective damage to the proximal tubule. The differential pathways of metabolic activation of DNT appear to apply to the proximal tubule of the kidney and to the urothelium of the renal pelvis and lower urinary tract as target tissues of carcinogenicity.

Pathological excretion patterns of urinary proteins in miners highly exposed to dinitrotoluene

A cohort of 161 underground miners who had been highly exposed to dinitrotoluene (DNT) in the copper-mining industry of the former German Democratic Republic was reinvestigated for signs of subclinical renal damage. The study included a screening of urinary proteins excreted by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and quantitations of the specific urinary proteins α 1-microglobulin and glutathione-S-transferase α (GST α) as biomarkers for damage of the proximal tubule and glutathione-S-transferase π (GST π) for damage of the distal tubule. The exposures were categorized semiquantitatively (low, medium, high, and very high), according to the type and duration of professional contact with DNT. A straight dose-dependence of pathological protein excretion patterns with the semiquantitative ranking of DNT exposure was seen. Most of the previously reported cancer cases of the urinary tract, especially those in the higher exposed groups, were confined to pathological urinary protein excretion patterns. The damage from DNT was directed toward the tubular system. In many cases, the appearance of Tamm-Horsfall protein, a 105-kD protein marker, was noted. Data on the biomarkers α 1-microglobulin, GST α, and GST π consistently demonstrated a dose-dependent increase in tubular damage, which confirmed the results of screening by SDS-PAGE and clearly indicated a nephrotoxic effect of DNT under the given conditions of exposure. Within the cluster of cancer patients observed among the DNT-exposed workers, only in exceptional cases were normal biomarker excretions found.

Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol

The coffee components kahweol and cafestol (K/C) have been reported to protect the colon and other organs of the rat against the formation of DNA adducts by 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and aflatoxin B1. PhIP is a cooked-food mutagen to which significant human exposure and a role in colon cancer etiology are attributed, and, interestingly, such cancers appear to develop at a lower rate in consumers of coffees with high amounts of K/C. Earlier studies in rodent liver have shown that a key role in the chemopreventive effect of K/C is likely to be due to the potential of these compounds to induce the detoxification of xenobiotics by glutathione transferase (GST) and to enhance the synthesis of the corresponding co-factor glutathione. However, mutagens like PhIP may also be detoxified by UDP-glucuronosyl transferase (UDPGT) for which data are lacking regarding a potential effect of K/C. Therefore, in the present study, we investigated the effect of K/C on UDPGT and, concomitantly, we studied overall GST and the pattern of individual GST classes, particularly GST-θ, which was not included in earlier experiments. In addition, we analyzed the organ-dependence of these potentially chemopreventive effects. K/C was fed to male F344 rats at 0.122% in the chow for 10 days. Enzyme activities in liver, kidney, lung, colon, salivary gland, pancreas, testis, heart and spleen were quantified using five characteristic substrates and the hepatic protein pattern of GST classes α, μ, and π was studied with affnity chromatography/HPLC. Our study showed that K/C is not only capable of increasing overall GST and GST classes α, μ, and π but also of enhancing UDGPT and GST-θ. All investigated K/C effects were strongest in liver and kidney, and some response was seen in lung and colon but none in the other organs. In summary, our results show that K/C treatment leads to a wide spectrum of increases in phase II detoxification enzymes. Notably, these effects occurred preferentially in the well perfused organs liver and kidney, which may thus not only contribute to local protection but also to anti-carcinogenesis in distant, less stimulated organs such as the colon.

Stop-signal response inhibition in schizophrenia : Behavioural, event-related potential and functional neuroimaging data

Inhibitory control deficits are well documented in schizophrenia, supported by impairment in an established measure of response inhibition, the stop-signal reaction time (SSRT). We investigated the neural basis of this impairment by comparing schizophrenia patients and controls matched for age, sex and education on behavioural, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) indices of stop-signal task performance. Compared to controls, patients exhibited slower SSRT and reduced right inferior frontal gyrus (rIFG) activation, but rIFG activation correlated with SSRT in both groups. Go stimulus and stop-signal ERP components (N1/P3) were smaller in patients, but the peak latencies of stop-signal N1 and P3 were also delayed in patients, indicating impairment early in stop-signal processing. Additionally, response-locked lateralised readiness potentials indicated response preparation was prolonged in patients. An inability to engage rIFG may predicate slowed inhibition in patients, however multiple spatiotemporal irregularities in the networks underpinning stop-signal task performance may contribute to this deficit.

Twitter data: what do they represent?

Scholarly research into the uses of social media has become a major area of growth in recent years, as the adoption of social media for public communication itself has continued apace. While social media platforms provide ready avenues for data access through their Application Programming interfaces, it is increasingly important to think through exactly what these data represent, and what conclusions about the role of social media in society the research which is based on such data therefore enables. This article explores these issues especially for one of the currently leading social media platforms: Twitter.