A systematic review of geographical variation in access to chemotherapy

BACKGROUND: Rising cancer incidence, the cost of cancer pharmaceuticals and the introduction of the Cancer Drugs Fund in England, but not other United Kingdom(UK) countries means evidence of ‘postcode prescribing’ in cancer is important. There have been no systematic reviews considering access to cancer drugs by geographical characteristics in the UK. METHODS: Studies describing receipt of cancer drugs, according to healthcare boundaries (e.g. cancer network [UK]) were identified through a systematic search of electronic databases and grey literature. Due to study heterogeneity a meta-analysis was not possible and a narrative synthesis was performed. RESULTS: 8,780 unique studies were identified and twenty-six included following a systematic search last updated in 2015. The majority of papers demonstrated substantial variability in the likelihood of receiving chemotherapy between hospitals, health authorities, cancer networks and UK countries (England and Wales). After case-mix adjustment, there was up to a 4–5 fold difference in chemotherapy utilisation between the highest and lowest prescribing cancer networks. There was no strong evidence that rurality or distance travelled were associated with the likelihood of receiving chemotherapy and conflicting evidence for an effect of travel time. CONCLUSIONS: Considerable variation in chemotherapy prescribing between healthcare boundaries has been identified. The absence of associations with natural geographical characteristics (e.g. rurality) and receipt of chemotherapy suggests that local treatment habits, capacity and policy are more influential. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-015-2026-y) contains supplementary material, which is available to authorized users

Genes influencing milk production traits predominantly affect one of four biological pathways

In this study we introduce a method that accounts for false positive and false negative results in attempting to estimate the true proportion of quantitative trait loci that affect two different traits. This method was applied to data from a genome scan that was used to detect QTL for three independent milk production traits, Australian Selection Index (ASI), protein percentage (P%) and fat percentage corrected for protein percentage (F% – P%). These four different scenarios are attributed to four biological pathways: QTL that (1) increase or decrease total mammary gland production (affecting ASI only); (2) increase or decrease lactose synthesis resulting in the volume of milk being changed but without a change in protein or fat yield (affecting P% only); (3) increase or decrease protein synthesis while milk volume remains relatively constant (affecting ASI and P% in the same direction); (4) increase or decrease fat synthesis while the volume of milk remains relatively constant (affecting F% – P% only). The results indicate that of the positions that detected a gene, most affected one trait and not the others, though a small proportion (2.8%) affected ASI and P% in the same direction

Equity of access to treatment on the Cancer Drugs Fund:A missed opportunity for cancer research?

AbstractUsing mixed-methods, we investigated the CDF in the South West of England (3193 cancer patients treated through the CDF, April 1st 2011–March 31st 2013) for evidence of: (1) equitable access across socioeconomic groups, age groups, sex, and Cancer Network; (2) time-to-treatment by socioeconomic group; and (3) the perception of the CDF as fair, using semi-structured interviews with oncology consultants.There was no evidence of inequitable access to anti-cancer therapy for those in more deprived areas. For all cancer types, there was a lower proportion of women in the CDF cohort than in the Cancer Registry reference population (e.g., melanoma, CDF 36.8% female, reference population 48.7%; difference 11.9%, 95% CI 3.1–20.7%). There was a lower proportion of older patients in the CDF compared with the reference population (e.g., colorectal cancer, CDF 6.9% ≥80 years, reference population 30.1%; difference 23.2%, 95% CI 20.2–26.2%). Interviewed oncologists felt differences in performance status, not age, influenced referral to the CDF, with neither deprivation, nor gender contributing.Our study suggests that the CDF has differential access by age and sex, but not by deprivation. The absence of high quality CDF data represents a missed opportunity to fully evaluate equity of access and the real-world costs and outcomes of novel anti-cancer drugs

La ionosfera: comunicare... naturalmente!

La ionosfera è la parte della media-alta atmosfera compresa tra i 60 e i 1000 km di quota. Essa è caratterizzata da una concentrazione di elettroni tale da modificare la propagazione delle onde radio che la attraversano

AVERT2(a very early rehabilitation trial, a very effective reproductive trigger): retrospective observational analysis of the number of babies born to trial staff

Objective: To report the number of participants needed to recruit per baby born to trial staff during AVERT, a large international trial on acute stroke, and to describe trial management consequences. Design: Retrospective observational analysis. Setting: 56 acute stroke hospitals in eight countries. Participants: 1074 trial physiotherapists, nurses, and other clinicians. Outcome measures: Number of babies born during trial recruitment per trial participant recruited. Results: With 198 site recruitment years and 2104 patients recruited during AVERT, 120 babies were born to trial staff. Births led to an estimated 10% loss in time to achieve recruitment. Parental leave was linked to six trial site closures. The number of participants needed to recruit per baby born was 17.5 (95% confidence interval 14.7 to 21.0); additional trial costs associated with each birth were estimated at 5736 Australian dollars on average. Conclusion: The staff absences registered in AVERT owing to parental leave led to delayed trial recruitment and increased costs, and should be considered by trial investigators when planning research and estimating budgets. However, the celebration of new life became a highlight of the annual AVERT collaborators’ meetings and helped maintain a cohesive collaborative group

Effects of Surface Geology on Seismic Ground Motion Deduced from Ambient-Noise Measurements in the Town of Avellino, Irpinia Region (Italy)

The effects of surface geology on ground motion provide an important tool in seismic hazard studies. It is well known that the presence of soft sediments can cause amplification of the ground motion at the surface, particularly when there is a sharp impedance contrast at shallow depth. The town of Avellino is located in an area characterised by high seismicity in Italy, about 30 km from the epicentre of the 23 November 1980, Irpinia earthquake (M = 6.9). No earthquake recordings are available in the area. The local geology is characterised by strong heterogeneity, with impedance contrasts at depth. We present the results from seismic noise measurements carried out in the urban area of Avellino to evaluate the effects of local geology on the seismic ground motion. We computed the horizontal-to-vertical (H/V) noise spectral ratios at 16 selected sites in this urban area for which drilling data are available within the first 40 m of depth. A Rayleigh wave inversion technique using the peak frequencies of the noise H/V spectral ratios is then presented for estimating Vs models, assuming that the thicknesses of the shallow soil layers are known. The results show a good correspondence between experimental and theoretical peak frequencies, which are interpreted in terms of sediment resonance. For one site, which is characterised by a broad peak in the horizontal-to-vertical spectral-ratio curve, simple one-dimensional modelling is not representative of the resonance effects. Consistent variations in peak amplitudes are seen among the sites. A site classification based on shear-wave velocity characteristics, in terms of Vs30, cannot explain these data. The differences observed are better correlated to the impedance contrast between the sediments and basement. A more detailed investigation of the physical parameters of the subsoil structure, together with earthquake data, are desirable for future research, to confirm these data in terms of site response

Neutrophil Elastase Promotes Interleukin-1 beta Secretion from Human Coronary Endothelium

The endothelium is critically involved in the pathogenesis of atherosclerosis by producing pro-inflammatory mediators, including IL-1β. Coronary arteries from patients with ischemic heart disease express large amounts of IL-1β in the endothelium. However, the mechanism by which endothelial cells (ECs) release IL-1β remains to be elucidated. We investigated neutrophil elastase (NE), a potent serine protease detected in vulnerable areas of human carotid plaques, as a potential “trigger” for IL-1β processing and release. This study tested the hypothesis that NE potentiates the processing and release of IL-1β from human coronary endothelium. We found that NE cleaves the pro-isoform of IL-1β in ECs and causes significant secretion of bioactive IL-1β via extracellular vesicles. This release was attenuated significantly by inhibition of neutrophil elastase but not caspase-1. Transient increases in intracellular Ca2+ levels were observed prior to secretion. Inside ECs, and after NE treatment only, IL-1β was detected within LAMP-1-positive multivesicular bodies. The released vesicles contained bioactive IL-1β. In vivo, in experimental atherosclerosis, NE was detected in mature atherosclerotic plaques, predominantly in the endothelium, alongside IL-1β. This study reveals a novel mechanistic link between NE expression in atherosclerotic plaques and concomitant pro-inflammatory bioactive IL-1β secretion from ECs. This could reveal additional potential anti-IL-1β therapeutic targets and provide further insights into the inflammatory process by which vascular disease develops

Expression of mitochondrial protein genes encoded by nuclear and mitochondrial genomes correlate with energy metabolism in dairy cattle

Background Mutations in the mitochondrial genome have been implicated in mitochondrial disease, often characterized by impaired cellular energy metabolism. Cellular energy metabolism in mitochondria involves mitochondrial proteins (MP) from both the nuclear (NuMP) and mitochondrial (MtMP) genomes. The expression of MP genes in tissues may be tissue specific to meet varying specific energy demands across the tissues. Currently, the characteristics of MP gene expression in tissues of dairy cattle are not well understood. In this study, we profile the expression of MP genes in 29 adult and six foetal tissues in dairy cattle using RNA sequencing and gene expression analyses: particularly differential gene expression and co-expression network analyses. Results MP genes were differentially expressed (DE; over-expressed or under-expressed) across tissues in cattle. All 29 tissues showed DE NuMP genes in varying proportions of over-expression and under-expression. On the other hand, DE of MtMP genes was observed in < 50% of tissues and notably MtMP genes within a tissue was either all over-expressed or all under-expressed. A high proportion of NuMP (up to 60%) and MtMP (up to 100%) genes were over-expressed in tissues with expected high metabolic demand; heart, skeletal muscles and tongue, and under-expressed (up to 45% of NuMP, 77% of MtMP genes) in tissues with expected low metabolic rates; leukocytes, thymus, and lymph nodes. These tissues also invariably had the expression of all MtMP genes in the direction of dominant NuMP genes expression. The NuMP and MtMP genes were highly co-expressed across tissues and co-expression of genes in a cluster were non-random and functionally enriched for energy generation pathway. The differential gene expression and co-expression patterns were validated in independent cow and sheep datasets. Conclusions The results of this study support the concept that there are biological interaction of MP genes from the mitochondrial and nuclear genomes given their over-expression in tissues with high energy demand and co-expression in tissues. This highlights the importance of considering MP genes from both genomes in future studies related to mitochondrial functions and traits related to energy metabolism