Weight-modification trials in older adults: what should the outcome measure be?

BACKGROUND: Overweight older adults are often counseled to lose weight, even though there is little evidence of excess mortality in that age group. Overweight and underweight may be more associated with health status than with mortality, but few clinical trials of any kind have been based on maximizing years of healthy life (YHL), as opposed to years of life (YOL). OBJECTIVE: This paper examines the relationship of body mass index (BMI) to both YHL and YOL. Results were used to determine whether clinical trials of weight-modification based on improving YHL would be more powerful than studies based on survival. DESIGN: We used data from a cohort of 4,878 non-smoking men and women aged 65–100 at baseline (mean age 73) and followed 7 years. We estimated mean YHL and YOL in four categories of BMI: underweight, normal, overweight, and obese. RESULTS: Subjects averaged 6.3 YOL and 4.6 YHL of a possible 7 years. Both measures were higher for women and whites. For men, none of the BMI groups was significantly different from the normal group on either YOL or YHL. For women, the obese had significantly lower YHL (but not YOL) than the normals, and the underweight had significantly lower YOL and YHL. The overweight group was not significantly different from the normal group on either measure. CONCLUSIONS: Clinical trials of weight loss interventions for obese older women would require fewer participants if YHL rather than YOL was the outcome measure. Interventions for obese men or for the merely overweight are not likely to achieve differences in either YOL or YHL. Evaluations of interventions for the underweight (which would presumably address the causes of their low weight) may be conducted efficiently using either outcome measure

Comparative transcriptional profiling of the limbal epithelial crypt demonstrates its putative stem cell niche characteristics

<p>Abstract</p> <p>Background</p> <p>The Limbal epithelial crypt (LEC) is a solid cord of cells, approximately 120 microns long. It arises from the undersurface of interpalisade rete ridges of the limbal palisades of Vogt and extends deeper into the limbal stroma parallel or perpendicular to the palisade. There are up to 6 or 7 such LEC, variably distributed along the limbus in each human eye.</p> <p>Morphological and immunohistochemical studies on the limbal epithelial crypt (LEC) have demonstrated the presence of limbal stem cells in this region. The purpose of this microarray study was to characterise the transcriptional profile of the LEC and compare with other ocular surface epithelial regions to support our hypothesis that LEC preferentially harbours stem cells (SC).</p> <p>Results</p> <p>LEC was found to be enriched for SC related Gene Ontology (GO) terms including those identified in quiescent adult SC, however similar to cornea, limbus had significant GO terms related to proliferating SC, transient amplifying cells (TAC) and differentiated cells (DC). LEC and limbus were metabolically dormant with low protein synthesis and downregulated cell cycling. Cornea had upregulated genes for cell cycling and self renewal such as <it>FZD7, BTG1, CCNG</it>, and <it>STAT3 </it>which were identified from other SC populations. Upregulated gene expression for growth factors, cytokines, WNT, Notch, TGF-Beta pathways involved in cell proliferation and differentiation were noted in cornea. LEC had highest number of expressed sequence tags (ESTs), downregulated and unknown genes, compared to other regions. Genes expressed in LEC such as <it>CDH1, SERPINF1, LEF1, FRZB1</it>, <it>KRT19, SOD2, EGR1 </it>are known to be involved in SC maintenance. Genes of interest, in LEC belonging to the category of cell adhesion molecules, WNT and Notch signalling pathway were validated with real-time PCR and immunofluorescence.</p> <p>Conclusions</p> <p>Our transcriptional profiling study identifies the LEC as a preferential site for limbal SC with some characteristics suggesting that it could function as a 'SC niche' supporting quiescent SC. It also strengthens the evidence for the presence of "transient cells" in the corneal epithelium. These cells are immediate progeny of SC with self-renewal capacity and could be responsible for maintaining epithelial turn over in normal healthy conditions of the ocular surface (OS). The limbus has mixed population of differentiated and undifferentiated cells.</p

Perceptions of Support Among Older African American Cancer Survivors

To explore the perceived social support needs among older adult African American cancer survivors

Cancer symptom awareness and barriers to symptomatic presentation in England – Are we clear on cancer?

Background: Low cancer awareness may contribute to delayed diagnosis and poor cancer survival. We aimed to quantify socio-demographic differences in cancer symptom awareness and barriers to symptomatic presentation in the English population. Methods: Using a uniquely large data set (n=49?270), we examined the association of cancer symptom awareness and barriers to presentation with age, gender, marital status and socio-economic position (SEP), using logistic regression models to control for confounders. Results: The youngest and oldest, the single and participants with the lowest SEP recognised the fewest cancer symptoms, and reported most barriers to presentation. Recognition of nine common cancer symptoms was significantly lower, and embarrassment, fear and difficulties in arranging transport to the doctor’s surgery were significantly more common in participants living in the most deprived areas than in the most affluent areas. Women were significantly more likely than men to both recognise common cancer symptoms and to report barriers. Women were much more likely compared with men to report that fear would put them off from going to the doctor. Conclusions: Large and robust socio-demographic differences in recognition of some cancer symptoms, and perception of some barriers to presentation, highlight the need for targeted campaigns to encourage early presentation and improve cancer outcomes

Improving health care quality for racial/ethnic minorities: a systematic review of the best evidence regarding provider and organization interventions

BACKGROUND: Despite awareness of inequities in health care quality, little is known about strategies that could improve the quality of healthcare for ethnic minority populations. We conducted a systematic literature review and analysis to synthesize the findings of controlled studies evaluating interventions targeted at health care providers to improve health care quality or reduce disparities in care for racial/ethnic minorities. METHODS: We performed electronic and hand searches from 1980 through June 2003 to identify randomized controlled trials or concurrent controlled trials. Reviewers abstracted data from studies to determine study characteristics, results, and quality. We graded the strength of the evidence as excellent, good, fair or poor using predetermined criteria. The main outcome measures were evidence of effectiveness and cost of strategies to improve health care quality or reduce disparities in care for racial/ethnic minorities. RESULTS: Twenty-seven studies met criteria for review. Almost all (n = 26) took place in the primary care setting, and most (n = 19) focused on improving provision of preventive services. Only two studies were designed specifically to meet the needs of racial/ethnic minority patients. All 10 studies that used a provider reminder system for provision of standardized services (mostly preventive) reported favorable outcomes. The following quality improvement strategies demonstrated favorable results but were used in a small number of studies: bypassing the physician to offer preventive services directly to patients (2 of 2 studies favorable), provider education alone (2 of 2 studies favorable), use of a structured questionnaire to assess adolescent health behaviors (1 of 1 study favorable), and use of remote simultaneous translation (1 of 1 study favorable). Interventions employing more than one main strategy were used in 9 studies with inconsistent results. There were limited data on the costs of these strategies, as only one study reported cost data. CONCLUSION: There are several promising strategies that may improve health care quality for racial/ethnic minorities, but a lack of studies specifically targeting disease areas and processes of care for which disparities have been previously documented. Further research and funding is needed to evaluate strategies designed to reduce disparities in health care quality for racial/ethnic minorities

The Relevance of Fatalism in the Study of Latinas’ Cancer Screening Behavior: A Systematic Review of the Literature

# The Author(s) 2010. This article is published with open access at Springerlink.com Background Fatalism has been identified as a dominant belief among Latinos and is believed to act as a barrier to cancer prevention. However, controversy exists over the utility of the construct in explaining health disparities experienced by disadvantaged populations above the influence of structural barriers such as low socioeconomic status (SES) and limited access to health care. Purpose This paper reviews the empirical research on fatalism and Latinas ’ participation in cancer screening in an attempt to determine whether fatalism predicts participation in cancer screening after accounting for structural barriers

Cataract surgery by appointment – a pilot study

BACKGROUND: "Cataract Surgery by Appointment" is a new method of delivery of cataract surgery that reduces the time a patient spends in hospital by their direct arrival at the operating theatre, having self-prepared for surgery, thus avoiding admission to the ward or time spent in the Day Case Unit. The patient can stay as little as 20 minutes from their arrival to going home. We describe the process in detail, and seek to evaluate the visual outcome, safety and patient satisfaction of same. METHODS: Visual outcome and safety data were obtained from patients' medical records, prospectively. Patients were also surveyed by a questionnaire to determine their satisfaction with the service and viability as a prospect for providing a more efficient cataract surgery service. RESULTS: In 2002, fifty-one eyes of 39 consecutive patients underwent "Cataract Surgery by Appointment". There were 16 male and 23 female. The pre-operative best-corrected visual acuity was 6/9 or better in 17 (33%) eyes. The post-operative best-corrected visual acuity was 6/9 or better in 44 (86%) eyes. There were no per-operative complications. Post-operative complications occurred in 3 (6%) eyes. The average number of days from surgery to final discharge was 14.5 days. Twenty-eight (72%) completed questionnaires were returned. The results show that the majority of patients were satisfied with their overall experience of this mode of delivery for cataract surgery. CONCLUSION: "Cataract Surgery by Appointment" performed under local anaesthesia by a skilled ophthalmic surgeon appears to be safe and effective for highly selected cases. This method of delivery gave a high level of patient satisfaction, and is the ultimate form of day case cataract surgery. The method may gain widespread use should per-operative intracameral pupil dilatation prove to be effective and acceptable. Attention should be paid to risk-stratification, so complex cases are allocated more time on the operating list

Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer

Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit

Optimised laser microdissection of the human ocular surface epithelial regions for microarray studies

Background The most important challenge of performing insitu transcriptional profiling of the human ocular surface epithelial regions is obtaining samples in sufficient amounts, without contamination from adjacent tissue, as the region of interest is microscopic and closely apposed to other tissues regions. We have effectively collected ocular surface (OS) epithelial tissue samples from the Limbal Epithelial Crypt (LEC), limbus, cornea and conjunctiva of post-mortem cadaver eyes with laser microdissection (LMD) technique for gene expression studies with spotted oligonucleotide microarrays and Gene 1.0 ST arrays. Methods Human donor eyes (4 pairs for spotted oligonucleotide microarrays, 3 pairs for Gene 1.0 ST arrays) consented for research were included in this study with due ethical approval of the Nottingham Research Ethics Committee. Eye retrieval was performed within 36 hours of post-mortem period. The dissected corneoscleral buttons were immersed in OCT media and frozen in liquid nitrogen and stored at −80°C till further use. Microscopic tissue sections of interest were taken on PALM slides and stained with Toluidine Blue for laser microdissection with PALM microbeam systems. Optimisation of the laser microdissection technique was crucial for efficient and cost effective sample collection. Results The starting concentration of RNA as stipulated by the protocol of microarray platforms was taken as the cut-off concentration of RNA samples in our studies. The area of LMD tissue processed for spotted oligonucleotide microarray study ranged from 86,253 μm2 in LEC to 392,887 μm2 in LEC stroma. The RNA concentration of the LMD samples ranged from 22 to 92 pg/μl. The recommended starting concentration of the RNA samples used for Gene 1.0 ST arrays was 6 ng/5 μl. To achieve the desired RNA concentration the area of ocular surface epithelial tissue sample processed for the Gene 1.0 ST array experiments was approximately 100,0000 μm2 to 130,0000 μm2. RNA concentration of these samples ranged from 10.88 ng/12 μl to 25.8 ng/12 μl, with the RNA integrity numbers (RIN) for these samples from 3.3 to 7.9. RNA samples with RIN values below 2, that had failed to amplify satisfactorily were discarded. Conclusions The optimised protocol for sample collection and laser microdissection improved the RNA yield of the insitu ocular surface epithelial regions for effective microarray studies on spotted oligonucleotide and affymetrix platforms