Socio-demographic inequalities in stage of cancer diagnosis: Evidence from patients with female breast,lung, colon, rectal, prostate, renal, bladder, melanoma, ovarian and endometrial cancer

This is the final published version. Available from Oxford University Press via the DOI in this record.Background: Understanding socio-demographic inequalities in stage at diagnosis can inform priorities for cancer control. Patients and methods: We analysed data on the stage at diagnosis of East of England patients diagnosed with any of 10 common cancers, 2006-2010. Stage information was available on 88 657 of 98 942 tumours (89.6%). Results: Substantial socio-demographic inequalities in advanced stage at diagnosis (i.e. stage III/IV) existed for seven cancers, but their magnitude and direction varied greatly by cancer: advanced stage at diagnosis was more likely for older patients with melanoma but less likely for older patients with lung cancer [odds ratios for 75-79 versus 65-69 1.60 (1.38-1.86) and 0.83 (0.77-0.89), respectively]. Deprived patients were more likely to be diagnosed in advanced stage for melanoma, prostate, endometrial and (female) breast cancer: odds ratios (most versus least deprived quintile) from 2.24 (1.66-3.03) for melanoma to 1.31 (1.15-1.49) for breast cancer. In England, elimination of sociodemographic inequalities in stage at diagnosis could decrease the number of patients with cancer diagnosed in advanced stage by 5600 annually. Conclusions: There are substantial socio-demographic inequalities in stage at diagnosis for most cancers. Earlier detection interventions and policies can be targeted on patients at higher risk of advanced stage diagnosis. ©The Author 2012.National Institute for Health Research (NIHR

An economic comparison of hospital-based and community-based glaucoma clinics

INTRODUCTION: We have established one model for community care of glaucoma clinic patients. Community optometrists received training and accreditation in glaucoma care. Once qualified they alternated between running half day glaucoma clinics in their own High Street practices and assisting in a hospital-based glaucoma clinic session. This paper reports the cost of this model. METHODS: Micro-costing was undertaken for the hospital clinic. A consensus meeting was held to agree costs for community clinics involving all optometrists in the project along with representatives of the multiple chain optometry practices who had participated. Costs to patients both indirect and direct were calculated following structured interviews of 197 patients attending hospital clinics and 194 attending community clinics. RESULTS: The estimated cost per patient attendance to the hospital clinic was £63.91 and the estimated cost per attendance to the community clinic was £145.62. For patients the combined direct and indirect cost to attend the hospital clinic was £6.15 and the cost to attend the community clinic £5.91. DISCUSSION: The principal reason for the higher cost in the community clinic was higher overhead costs in the community. Re-referral to the hospital system only occurred for 9% of patients and was not a large contribution to the increased cost. Time requested to next appointment was similar for the two clinics. Sensitivity analysis shows a strong effect of increasing patients seen per clinic. It would, however, require 25 patients to be seen per clinician per day in the community in order to make the costs comparable

Ocular injuries in survivors of improvised explosive devices (IED) in commuter trains

<p>Abstract</p> <p>Background</p> <p>Ocular injuries are common in survivors of terror incidents that involve the use of explosive materials. These explosives are commonly of a High Explosive type (HE) and may be fashioned into improvised explosive devices (IED) that incorporate additional materials to maximise trauma and injuries. Serial IED explosions have occurred in commuter trains in several cities including London and Madrid but data on ocular injuries is limited. We report the ocular injuries of the survivors of a series of IED explosions in crowded commuter trains.</p> <p>Methods</p> <p>28 patients (56 eyes, 28 male, ages ranging from 22 to 52 years (mean 35.27 years) were screened in the triage area or the Intensive Care Unit (ICU). Testing included bedside visual acuity testing, torchlight examination of the anterior segment and dilated (or if necessary, undilated) fundus examination. Selected patients underwent B-scan examination, magnetic resonance imaging of the brain, orbits and the optic nerves or visual evoked potential assessment. The injuries, investigations and procedures were entered into the patient's case sheet as well as into a standardised format suggested by the Indian eye injury registry (IER).</p> <p>Results</p> <p>16 of 28 patients (57.1%) had ocular injuries whereas 12 (42.8%) were found to be normal. Injuries were seen unilaterally in 10 patients and bilaterally in six yielding a total of 22 injured eyes. The common injuries were periorbital haemorrhages (09 eyes, 40%); first or second degree burns to the upper or lower lids (seen in 07 eyes, 31.8 %) and corneal injuries (seen in 08 eyes, 36.3%). Open globe injuries were seen in two eyes of two patients (09%). One patient (4.5%) had a traumatic optic neuropathy.</p> <p>Conclusion</p> <p>Ophthalmologists and traumatologists should be aware of these patterns of ocular injuries. Protocols need to include the screening of large numbers of patients in a short time, diagnostic tests (B scan, visual evoked potential (VEP) etc) and early surgery preferably at the initial triage itself as most of the serious injuries in our studies had been missed or not treated at an initial assessment.</p

Predictors of failed attendances in a multi-specialty outpatient centre using electronic databases.

BACKGROUND: Failure to keep outpatient medical appointments results in inefficiencies and costs. The objective of this study is to show the factors in an existing electronic database that affect failed appointments and to develop a predictive probability model to increase the effectiveness of interventions. METHODS: A retrospective study was conducted on outpatient clinic attendances at Tan Tock Seng Hospital, Singapore from 2000 to 2004. 22864 patients were randomly sampled for analysis. The outcome measure was failed outpatient appointments according to each patient's latest appointment. RESULTS: Failures comprised of 21% of all appointments and 39% when using the patients' latest appointment. Using odds ratios from the mutliple logistic regression analysis, age group (0.75 to 0.84 for groups above 40 years compared to below 20 years), race (1.48 for Malays, 1.61 for Indians compared to Chinese), days from scheduling to appointment (2.38 for more than 21 days compared to less than 7 days), previous failed appointments (1.79 for more than 60% failures and 4.38 for no previous appointments, compared with less than 20% failures), provision of cell phone number (0.10 for providing numbers compared to otherwise) and distance from hospital (1.14 for more than 14 km compared to less than 6 km) were significantly associated with failed appointments. The predicted probability model's diagnostic accuracy to predict failures is more than 80%. CONCLUSION: A few key variables have shown to adequately account for and predict failed appointments using existing electronic databases. These can be used to develop integrative technological solutions in the outpatient clinic

Dynein structure and power stroke

Dynein ATPases are microtubule motors that are critical to diverse processes such as vesicle transport and the beating of sperm tails; however, their mechanism of force generation is unknown. Each dynein comprises a head, from which a stalk and a stem emerge. Here we use electron microscopy and image processing to reveal new structural details of dynein c, an isoform from Chlamydomonas reinhardtii flagella, at the start and end of its power stroke. Both stem and stalk are flexible, and the stem connects to the head by means of a linker approximately 10 nm long that we propose lies across the head. With both ADP and vanadate bound, the stem and stalk emerge from the head 10 nm apart. However, without nucleotide they emerge much closer together owing to a change in linker orientation, and the coiled-coil stalk becomes stiffer. The net result is a shortening of the molecule coupled to an approximately 15-nm displacement of the tip of the stalk. These changes indicate a mechanism for the dynein power stroke

Normal levels of p27Xic1 are necessary for somite segmentation and determining pronephric organ size

The Xenopus laevis cyclin dependent kinase inhibitor p27Xic1 has been shown to be involved in exit from the cell cycle and differentiation of cells into a quiescent state in the nervous system, muscle tissue, heart and retina. We show that p27Xic1 is expressed in the developing kidney in the nephrostomal regions. Using over-expression and morpholino oligonucleotide (MO) knock-down approaches we show normal levels of p27Xic1 regulate pronephros organ size by regulating cell cycle exit. Knock-down of p27Xic1 expression using a MO prevented myogenesis, as previously reported; an effect that subsequently inhibits pronephrogenesis. Furthermore, we show that normal levels of p27Xic1 are required for somite segmentation also through its cell cycle control function. Finally, we provide evidence to suggest correct paraxial mesoderm segmentation is not necessary for pronephric induction in the intermediate mesoderm. These results indicate novel developmental roles for p27Xic1, and reveal its differentiation function is not universally utilised in all developing tissues

Adapted motivational interviewing to improve the uptake of treatment for glaucoma in Nigeria: study protocol for a randomized controlled trial.

BACKGROUND: Glaucoma is a chronic eye disease associated with irreversible visual loss. In Africa, glaucoma patients often present late, with very advanced disease. One-off procedures, such as laser or surgery, are recommended in Africa because of lack of or poor adherence to medical treatment. However, acceptance of surgery is usually extremely low. To prevent blindness, adherence to treatment needs to improve, using acceptable, replicable and cost-effective interventions. After reviewing the literature and interviewing patients in Bauchi (Nigeria) motivational interviewing (MI) was selected as the intervention for this trial, with adaptation for glaucoma (MIG). MI is designed to strengthen personal motivation for, and commitment to a specific goal by eliciting and exploring a person's reasons for change within an atmosphere of acceptance and compassion. The aim of this study is to assess whether MIG increases the uptake of laser or surgery amongst glaucoma patients where this is the recommended treatment. The hypothesis is that MIG increases the uptake of treatment. This will be the first trial of MI in Africa. METHODS: This is a hospital based, single centre, randomized controlled trial of MIG plus an information sheet on glaucoma and its treatment (the latter being "standard care") compared with standard care alone for glaucoma patients where the treatment recommended is surgery or laser.Those eligible for the trial are adults aged 17 years and above who live within 200 km of Bauchi with advanced glaucoma where the examining ophthalmologist recommends surgery or laser. After obtaining written informed consent, participants will be randomly allocated to MIG plus standard care, or standard care alone. Motivational interviewing will be delivered in Hausa or English by one of two MIG trained personnel. One hundred and fifty participants will be recruited to each arm. The primary outcome is the proportion of participants undergoing laser or surgery within two months of the date given to re attend for the procedure. MIG quality will be assessed using the validated MI treatment integrity scale. DISCUSSION: Motivational interviewing may be an important tool to increase the acceptance of treatment for glaucoma. The approach is potentially scalable and may be useful for other chronic conditions in Africa. TRIAL REGISTRATION: ISRCTN79330571 (Controlled-Trials.com)

Systematic bias in real-world tonometry readings based on laterality?

AIMS: In research settings, the first eye examined tends to have a higher intraocular pressure (IOP) than the second. We sought to verify whether clinicians in Yorkshire, UK, measure IOP in right eyes before left and whether such behavioural factors affect IOP readings at the population level. METHODS: We observed 128 IOP measurements taken by 28 ophthalmologists using Goldmann applanation tonometry (GAT) over a 4-month period in 2018, recording which eye was examined first. All IOP measurements on electronic patient records for Leeds Teaching Hospitals NHS Trust, UK, between January 2002 and June 2017 were extracted, yielding IOP readings for 562,360 eyes, analysed for evidence of systematic bias in IOP measurement. RESULTS: Right eye IOP was measured before left in 112/128 observations (87.5% (95% CI: 75.2%-94.2%)). For IOP measured by GAT, there was no statistically significant difference (p = 0.121) between right and left eye IOP (mean IOP 16.95 and 16.96 mmHg, respectively). Even values of IOP were reported more frequently than odd values (136,503/214,628 (63.6%) were even). Identical IOP readings for both eyes were recorded in 124,392/254,380 patients (48.9%) who had both eyes measured. CONCLUSIONS: Our study found no IOP difference based on laterality, but strong evidence of certain trends associated with IOP measurement by GAT, such as a preference for even values and the same IOP being recorded for both left and right eyes. Such effects may be explained by behavioural aspects of GAT and suggest that there are substantial opportunities for improvement in the way GAT is utilised in real world settings

Imagable 4T1 model for the study of late stage breast cancer

<p>Abstract</p> <p>Background</p> <p>The 4T1 mouse mammary tumor cell line is one of only a few breast cancer models with the capacity to metastasize efficiently to sites affected in human breast cancer. Here we describe two 4T1 cell lines modified to facilitate analysis of tumor growth and metastasis and evaluation of gene function <it>in vivo</it>. New information regarding the involvement of innate and acquired immunity in metastasis and other characteristics of the model relevant to its use in the study of late stage breast cancer are reported.</p> <p>Methods</p> <p>The lines were engineered for stable expression of firefly luciferase to allow tracking and quantitation of the cells <it>in vivo</it>. Biophotonic imaging was used to characterize growth and metastasis of the lines <it>in vivo </it>and an improved gene expression approach was used to characterize the basis for the metastatic phenotype that was observed.</p> <p>Results</p> <p>Growth of cells at the primary site was biphasic with metastasis detected during the second growth phase 5–6 weeks after introduction of the cells. Regression of growth, which occurred in weeks 3–4, was associated with extensive necrosis and infiltration of leukocytes. Biphasic tumor growth did not occur in BALB/c SCID mice indicating involvement of an acquired immune response in the effect. Hematopoiesis in spleen and liver and elevated levels of circulating leukocytes were observed at week 2 and increased progressively until death at week 6–8. Gene expression analysis revealed an association of several secreted factors including colony stimulatory factors, cytokines and chemokines, acute phase proteins, angiogenesis factors and ECM modifying proteins with the 4T1 metastatic phenotype. Signaling pathways likely to be responsible for production of these factors were also identified.</p> <p>Conclusion</p> <p>The production of factors that stimulate angiogenesis and ECM modification and induce hematopoiesis, recruitment and activation of leukocytes suggest that 4T1 tumor cells play a more direct role than previously appreciated in orchestrating changes in the tumor environment conducive to tumor cell dissemination and metastasis. The new cell lines will greatly facilitate the study of late stage breast and preclinical assessment of cancer drugs and other therapeutics particularly those targeting immune system effects on tumor metastasis.</p