The role of adjuvant chemotherapy for patients with resected pancreatic cancer: Systematic review of randomized controlled trials and meta-analysis

Background: In patients undergoing surgery for resectable pancreatic cancer prognosis still remains poor. The role of adjuvant treatment strategies (including chemotherapy and chemoradiotherapy) following resection of pancreatic cancer remains controversial. Methods: A Medline-based literature search was undertaken to identify randomized controlled trials that evaluated adjuvant chemotherapy after complete macroscopic resection for cancer of the exocrine pancreas. Five trials of adjuvant chemotherapy were eligible and critically reviewed for this article. A meta-analysis (based on published data) was performed with survival (median survival time and 5-year survival rate) being the primary endpoint. Results: For the meta-analysis, 482 patients were allocated to the chemotherapy group and 469 patients to the control group. The meta-analysis estimate for prolongation of median survival time for patients in the chemotherapy group was 3 months (95% CI 0.3-5.7 months, p = 0.03). The difference in 5-year survival rate was estimated with 3.1% between the chemotherapy and the control group (95% CI -4.6 to 10.8%, p > 10.05). Conclusion: Currently available data from randomized trials indicate that adjuvant chemotherapy after resection of pancreatic cancer may substantially prolong disease-free survival and cause a moderate increase in overall survival. In the current meta-analysis, a significant survival benefit was only seen with regard to median survival, but not for the 5-year survival rate. The optimal chemotherapy regimen in the adjuvant setting as well as individualized treatment strategies (also including modern chemoradiotherapy regimens) still remain to be defined. Copyright (C) 2008 S. Karger AG, Basel

ER and HER2 expression are positively correlated in HER2 non-overexpressing breast cancer

PMCID: PMC3446380This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

A falls prevention programme to improve quality of life, physical function and falls efficacy in older people receiving home help services: study protocol for a randomised controlled trial

BACKGROUND: Falls and fall-related injuries in older adults are associated with great burdens, both for the individuals, the health care system and the society. Previous research has shown evidence for the efficiency of exercise as falls prevention. An understudied group are older adults receiving home help services, and the effect of a falls prevention programme on health-related quality of life is unclear. The primary aim of this randomised controlled trial is to examine the effect of a falls prevention programme on quality of life, physical function and falls efficacy in older adults receiving home help services. A secondary aim is to explore the mediating factors between falls prevention and health-related quality of life. METHODS: The study is a single-blinded randomised controlled trial. Participants are older adults, aged 67 or older, receiving home help services, who are able to walk with or without walking aids, who have experienced at least one fall during the last 12 months and who have a Mini Mental State Examination of 23 or above. The intervention group receives a programme, based on the Otago Exercise Programme, lasting 12 weeks including home visits and motivational telephone calls. The control group receives usual care. The primary outcome is health-related quality of life (SF-36). Secondary outcomes are leg strength, balance, walking speed, walking habits, activities of daily living, nutritional status and falls efficacy. All measurements are performed at baseline, following intervention at 3 months and at 6 months' follow-up. Sample size, based on the primary outcome, is set to 150 participants randomised into the two arms, including an estimated 15-20% drop out. Participants are recruited from six municipalities in Norway. DISCUSSION: This trial will generate new knowledge on the effects of an exercise falls prevention programme among older fallers receiving home help services. This knowledge will be useful for clinicians, for health managers in the primary health care service and for policy makers

The impact of loco-regional recurrences on metastatic progression in early-stage breast cancer: a multistate model

To study whether the effects of prognostic factors associated with the occurrence of distant metastases (DM) at primary diagnosis change after the incidence of loco-regional recurrences (LRR) among women treated for invasive stage I or II breast cancer. The study population consisted of 3,601 women, enrolled in EORTC trials 10801, 10854, or 10902 treated for early-stage breast cancer. Data were analysed in a multivariate, multistate model by using multivariate Cox regression models, including a state-dependent covariate. The presence of a LRR in itself is a significant prognostic risk factor (HR: 3.64; 95%-CI: 2.02-6.5) for the occurrence of DM. Main prognostic risk factors for a DM are young age at diagnosis (</=40: HR: 1.79; 95%-CI: 1.28-2.51), larger tumour size (HR: 1.58; 95%-CI: 1.35-1.84) and node positivity (HR: 2.00; 95%-CI: 1.74-2.30). Adjuvant chemotherapy is protective for a DM (HR: 0.66; 95%-CI: 0.55-0.80). After the occurrence of a LRR the latter protective effect has disappeared (P = 0.009). The presence of LRR in itself is a significant risk factor for DM. For patients who are at risk of developing LRR, effective local control should be the main target of therapy

Circulating markers of arterial thrombosis and late-stage age-related macular degeneration: a case-control study.

PURPOSE: The aim of this study was to examine the relation of late-stage age-related macular degeneration (AMD) with markers of systemic atherothrombosis. METHODS: A hospital-based case-control study of AMD was undertaken in London, UK. Cases of AMD (n=81) and controls (n=77) were group matched for age and sex. Standard protocols were used for colour fundus photography and to classify AMD; physical examination included height, weight, history of or treatment for vascular-related diseases and smoking status. Blood samples were taken for measurement of fibrinogen, factor VIIc (FVIIc), factor VIIIc, prothrombin fragment F1.2 (F1.2), tissue plasminogen activator, and von Willebrand factor. Odds ratios from logistic regression analyses of each atherothrombotic marker with AMD were adjusted for age, sex, and established cardiovascular disease risk factors, including smoking, blood pressure, body mass index, and total cholesterol. RESULTS: After adjustment FVIIc and possibly F1.2 were inversely associated with the risk of AMD; per 1 standard deviation increase in these markers the odds ratio were, respectively, 0.62 (95% confidence interval 0.40, 0.95) and 0.71 (0.46, 1.09). None of the other atherothrombotic risk factors appeared to be related to AMD status. There was weak evidence that aspirin is associated with a lower risk of AMD. CONCLUSIONS: This study does not provide strong evidence of associations between AMD and systematic markers of arterial thrombosis, but the potential effects of FVIIc, and F1.2 are worthy of further investigation

Family Planning Decisions, Perceptions and Gender Dynamics among Couples in Mwanza, Tanzania: A Qualitative Study.

Contraceptive use is low in developing countries which are still largely driven by male dominated culture and patriarchal values. This study explored family planning (FP) decisions, perceptions and gender dynamics among couples in Mwanza region of Tanzania. Twelve focus group discussions and six in-depth interviews were used to collect information from married or cohabiting males and females aged 18-49. The participants were purposively selected. Qualitative methods were used to explore family planning decisions, perceptions and gender dynamics among couples. A guide with questions related to family planning perceptions, decisions and gender dynamics was used. The discussions and interviews were tape-recorded, transcribed verbatim and analyzed manually and subjected to content analysis. Four themes emerged during the study. First, "risks and costs" which refer to the side effects of FP methods and the treatment of side -effects as well as the costs inherit in being labeled as an unfaithful spouse. Second, "male involvement" as men showed little interest in participating in family planning issues. However, the same men were mentioned as key decision-makers even on the number of children a couple should have and the child spacing of these children. Third, "gender relations and communication" as participants indicated that few women participated in decision-making on family planning and the number of children to have. Fourth, "urban-rural differences", life in rural favoring having more children than urban areas therefore, the value of children depended on the place of residence. Family Planning programs should adapt the promotion of communication as well as joint decision-making on FP among couples as a strategy aimed at enhancing FP use

Physical activity and health related quality of life

Copyright @ 2012 Anokye et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.This article has been made available through the Brunel Open Access Publishing Fund.BACKGROUND: Research on the relationship between Health Related Quality of Life (HRQoL) and physical activity (PA), to date, have rarely investigated how this relationship differ across objective and subjective measures of PA. The aim of this paper is to explore the relationship between HRQoL and PA, and examine how this relationship differs across objective and subjective measures of PA, within the context of a large representative national survey from England. METHODS: Using a sample of 5,537 adults (40–60 years) from a representative national survey in England (Health Survey for England 2008), Tobit regressions with upper censoring was employed to model the association between HRQoL and objective, and subjective measures of PA controlling for potential confounders. We tested the robustness of this relationship across specific types of PA. HRQoL was assessed using the summary measure of health state utility value derived from the EuroQol-5 Dimensions (EQ-5D) whilst PA was assessed via subjective measure (questionnaire) and objective measure (accelerometer- actigraph model GT1M). The actigraph was worn (at the waist) for 7 days (during waking hours) by a randomly selected sub-sample of the HSE 2008 respondents (4,507 adults – 16 plus years), with a valid day constituting 10 hours. Analysis was conducted in 2010. RESULTS: Findings suggest that higher levels of PA are associated with better HRQoL (regression coefficient: 0.026 to 0.072). This relationship is consistent across different measures and types of PA although differences in the magnitude of HRQoL benefit associated with objective and subjective (regression coefficient: 0.047) measures of PA are noticeable, with the former measure being associated with a relatively better HRQoL (regression coefficient: 0.072). CONCLUSION: Higher levels of PA are associated with better HRQoL. Using an objective measure of PA compared with subjective shows a relatively better HRQoL.This project was funded by the NIHR Health Technology Assessment programme (project number 08/72/01)

A Method of Drusen Measurement Based on the Geometry of Fundus Reflectance

BACKGROUND: The hallmarks of age-related macular degeneration, the leading cause of blindness in the developed world, are the subretinal deposits known as drusen. Drusen identification and measurement play a key role in clinical studies of this disease. Current manual methods of drusen measurement are laborious and subjective. Our purpose was to expedite clinical research with an accurate, reliable digital method. METHODS: An interactive semi-automated procedure was developed to level the macular background reflectance for the purpose of morphometric analysis of drusen. 12 color fundus photographs of patients with age-related macular degeneration and drusen were analyzed. After digitizing the photographs, the underlying background pattern in the green channel was leveled by an algorithm based on the elliptically concentric geometry of the reflectance in the normal macula: the gray scale values of all structures within defined elliptical boundaries were raised sequentially until a uniform background was obtained. Segmentation of drusen and area measurements in the central and middle subfields (1000 μm and 3000 μm diameters) were performed by uniform thresholds. Two observers using this interactive semi-automated software measured each image digitally. The mean digital measurements were compared to independent stereo fundus gradings by two expert graders (stereo Grader 1 estimated the drusen percentage in each of the 24 regions as falling into one of four standard broad ranges; stereo Grader 2 estimated drusen percentages in 1% to 5% intervals). RESULTS: The mean digital area measurements had a median standard deviation of 1.9%. The mean digital area measurements agreed with stereo Grader 1 in 22/24 cases. The 95% limits of agreement between the mean digital area measurements and the more precise stereo gradings of Grader 2 were -6.4 % to +6.8 % in the central subfield and -6.0 % to +4.5 % in the middle subfield. The mean absolute differences between the digital and stereo gradings 2 were 2.8 +/- 3.4% in the central subfield and 2.2 +/- 2.7% in the middle subfield. CONCLUSIONS: Semi-automated, supervised drusen measurements may be done reproducibly and accurately with adaptations of commercial software. This technique for macular image analysis has potential for use in clinical research

The systematic guideline review: method, rationale, and test on chronic heart failure

Background: Evidence-based guidelines have the potential to improve healthcare. However, their de-novo-development requires substantial resources-especially for complex conditions, and adaptation may be biased by contextually influenced recommendations in source guidelines. In this paper we describe a new approach to guideline development-the systematic guideline review method (SGR), and its application in the development of an evidence-based guideline for family physicians on chronic heart failure (CHF). Methods: A systematic search for guidelines was carried out. Evidence-based guidelines on CHF management in adults in ambulatory care published in English or German between the years 2000 and 2004 were included. Guidelines on acute or right heart failure were excluded. Eligibility was assessed by two reviewers, methodological quality of selected guidelines was appraised using the AGREE instrument, and a framework of relevant clinical questions for diagnostics and treatment was derived. Data were extracted into evidence tables, systematically compared by means of a consistency analysis and synthesized in a preliminary draft. Most relevant primary sources were re-assessed to verify the cited evidence. Evidence and recommendations were summarized in a draft guideline. Results: Of 16 included guidelines five were of good quality. A total of 35 recommendations were systematically compared: 25/35 were consistent, 9/35 inconsistent, and 1/35 un-rateable (derived from a single guideline). Of the 25 consistencies, 14 were based on consensus, seven on evidence and four differed in grading. Major inconsistencies were found in 3/9 of the inconsistent recommendations. We re-evaluated the evidence for 17 recommendations (evidence-based, differing evidence levels and minor inconsistencies) - the majority was congruent. Incongruity was found where the stated evidence could not be verified in the cited primary sources, or where the evaluation in the source guidelines focused on treatment benefits and underestimated the risks. The draft guideline was completed in 8.5 man-months. The main limitation to this study was the lack of a second reviewer. Conclusion: The systematic guideline review including framework development, consistency analysis and validation is an effective, valid, and resource saving-approach to the development of evidence-based guidelines

Polygenic risk score is associated with increased disease risk in 52 Finnish breast cancer families

The risk of developing breast cancer is increased in women with family history of breast cancer and particularly in families with multiple cases of breast or ovarian cancer. Nevertheless, many women with a positive family history never develop the disease. Polygenic risk scores (PRSs) based on the risk effects of multiple common genetic variants have been proposed for individual risk assessment on a population level. We investigate the applicability of the PRS for risk prediction within breast cancer families. We studied the association between breast cancer risk and a PRS based on 75 common genetic variants in 52 Finnish breast cancer families including 427 genotyped women and pedigree information on similar to 4000 additional individuals by comparing the affected to healthy family members, as well as in a case-control dataset comprising 1272 healthy population controls and 1681 breast cancer cases with information on family history. Family structure was summarized using the BOADICEA risk prediction model. The PRS was associated with increased disease risk in women with family history of breast cancer as well as in women within the breast cancer families. The odds ratio (OR) for breast cancer within the family dataset was 1.55 [95 % CI 1.26-1.91] per unit increase in the PRS, similar to OR in unselected breast cancer cases of the case-control dataset (1.49 [1.38-1.62]). High PRS-values were informative for risk prediction in breast cancer families, whereas for the low PRS-categories the results were inconclusive. The PRS is informative in women with family history of breast cancer and should be incorporated within pedigree-based clinical risk assessment.Peer reviewe