Exceptional responders in conservation.

Conservation operates within complex systems with incomplete knowledge of the system and the interventions utilized. This frequently results in the inability to find generally applicable methods to alleviate threats to Earth's vanishing wildlife. One approach used in medicine and the social sciences has been to develop a deeper understanding of positive outliers. Where such outliers share similar characteristics, they may be considered exceptional responders. We devised a 4-step framework for identifying exceptional responders in conservation: identification of the study system, identification of the response structure, identification of the threshold for exceptionalism, and identification of commonalities among outliers. Evaluation of exceptional responders provides additional information that is often ignored in randomized controlled trials and before-after control-intervention experiments. Interrogating the contextual factors that contribute to an exceptional outcome allow exceptional responders to become valuable pieces of information leading to unexpected discoveries and novel hypotheses

Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY

Birgegård G, Gascón P, Ludwig H. Evaluation of anaemia in patients with multiple myeloma and lymphoma: findings of the European CANCER ANAEMIA SURVEY. Objectives: Until recently, no prospective epidemiologic survey of lymphoma and multiple myeloma (L/MM) in European cancer patients had been conducted; furthermore, data on prevalence, incidence, and treatment patterns of L/MM were limited or unavailable. Here we define anemia prevalence, incidence, and treatment patterns, and identify anemia risk factors in European L/MM patients. Methods: Data for a subgroup of 2360 L/MM patients in the European Cancer Anaemia Survey (ECAS) were analyzed; variables included age, gender, tumor type/stage, cancer and anemia treatment, WHO performance status, and hemoglobin (Hb) levels. Results: 2316 patients were evaluable (1612 L and 704 MM). Anemia rate at enrollment was 52.5%. At enrollment, Hb levels correlated significantly with WHO scores (r = −0.306, P < 0.001). Anemia prevalence during ECAS was 72.9% (MM, 85.3%; non-Hodgkin's lymphoma, 77.9%; Hodgkin's disease, 57.4%); incidence in chemotherapy patients was 55.4%. Only 47.3% of patients anemic any time during ECAS received anemia treatment; overall Hb nadir for initiating treatment was 8.9 g/dL (epoetin, 9.5 g/dL; transfusion, 8.2 g/dL). Factors found to significantly (P < 0.03) increase anemia risk were low initial Hb, female gender, persistent/resistant disease, and platinum chemotherapy. Conclusions:L/MM patients have a high prevalence and incidence of anemia; however, anemia is not optimally treated. Anemia is common in L/MM patients and, given its known adverse impact on physical functioning and quality-of-life variables including fatigue and cognitive function, anemia management should be an integral part of their care. Predictive factors identified by ECAS may help clinicians develop optimal anemia treatment strategies for L/MM patients

Health care restructuring and family physician care for those who died of cancer

BACKGROUND: During the 1990s, health care restructuring in Nova Scotia resulted in downsized hospitals, reduced inpatient length of stay, capped physician incomes and restricted practice locations. Concurrently, the provincial homecare program was redeveloped and out-of-hospital cancer deaths increased from 20% (1992) to 30% (1998). These factors all pointed to a transfer of end-of-life inpatient hospital care to more community-based care. The purpose of this study was to describe the trends in the provision of Family Physician (FP) visits to advanced cancer patients in Nova Scotia (NS) during the years of health care restructuring. METHODS: Design Secondary multivariate analysis of linked population-based datafiles including the Queen Elizabeth II Health Sciences Centre Oncology Patient Information System (NS Cancer Registry, Vital Statistics), the NS Hospital Admissions/Separations file and the Medical Services Insurance Physician Services database. Setting Nova Scotia, an eastern Canadian province (population: 950,000). Subjects: All patients who died of lung, colorectal, breast or prostate cancer between April 1992 and March 1998 (N = 7,212). Outcome Measures Inpatient and ambulatory FP visits, ambulatory visits by location (office, home, long-term care facility, emergency department), time of day (regular hours, after hours), total length of inpatient hospital stay and number of hospital admissions during the last six months of life. RESULTS: In total, 139,641 visits were provided by family physicians: 15% of visits in the office, 10% in the home, 5% in the emergency department (ED), 5% in a long-term-care centre and 64% to hospital inpatients. There was no change in the rate of FP visits received for office, home and long-term care despite the fact that there were 13% fewer hospital admissions, and length of hospital stay declined by 21%. Age-sex adjusted estimates using negative binomial regression indicate a decline in hospital inpatient FP visits over time compared to 1992–93 levels (for 1997–98, adjusted RR = 0.88, 95%CI = 0.81–0.95) and an increase in FP ED visits (for 1997–98, adjusted RR = 1.18, 95%CI = 1.05–1.34). CONCLUSION: Despite hospital downsizing and fewer deaths occurring in hospitals, FP ambulatory visits (except for ED visits) did not rise correspondingly. Although such restructuring resulted in more people dying out of hospital, it does not appear FPs responded by providing more medical care to them in the community

TCF7L2 polymorphisms and inflammatory markers before and after treatment with fenofibrate

<p>Abstract</p> <p>Background</p> <p>Inflammation is implicated in causing diabetes. We tested whether transcription factor 7 like-2 (TCF7L2) gene polymorphisms (rs12255372 and rs7903146), consistently associated with type 2 diabetes, are associated with plasma concentrations of inflammatory markers before and after three weeks of daily treatment with fenofibrate.</p> <p>Methods</p> <p>Men and women in the Genetics of Lipid-Lowering Drugs and Diet Network study (n = 1025, age 49 ± 16 y) were included. All participants suspended use of lipid-lowering drugs for three weeks and were then given 160 mg/day of fenofibrate for three weeks. Inflammatory markers and lipids were measured before and after fenofibrate. ANOVA was used to test for differences across TCF7L2 genotypes.</p> <p>Results</p> <p>Under the additive or dominant model, there were no significant differences (<it>P </it>> 0.05) in the concentrations of inflammatory markers (hsCRP, IL-2, IL-6, TNF-α and MCP-1) across TCF7L2 genotypes in the period before or after treatment. For both rs12255372 and rs7903146, homozygote T-allele carriers had significantly higher (<it>P </it>< 0.05) post-fenofibrate concentrations of MCP-1 in the recessive model. No other significant associations were detected.</p> <p>Conclusion</p> <p>Overall these data show no association between TCF7L2 polymorphisms and the inflammatory markers suggesting that the effects of TCF7L2 on diabetes may not be via inflammation.</p

Cancer Risks near Nuclear Facilities: The Importance of Research Design and Explicit Study Hypotheses

BackgroundIn April 2010, the U.S. Nuclear Regulatory Commission asked the National Academy of Sciences to update a 1990 study of cancer risks near nuclear facilities. Prior research on this topic has suffered from problems in hypothesis formulation and research design.ObjectivesWe review epidemiologic principles used in studies of generic exposure–response associations and in studies of specific sources of exposure. We then describe logical problems with assumptions, formation of testable hypotheses, and interpretation of evidence in previous research on cancer risks near nuclear facilities.DiscussionAdvancement of knowledge about cancer risks near nuclear facilities depends on testing specific hypotheses grounded in physical and biological mechanisms of exposure and susceptibility while considering sample size and ability to adequately quantify exposure, ascertain cancer cases, and evaluate plausible confounders.ConclusionsNext steps in advancing knowledge about cancer risks near nuclear facilities require studies of childhood cancer incidence, focus on in utero and early childhood exposures, use of specific geographic information, and consideration of pathways for transport and uptake of radionuclides. Studies of cancer mortality among adults, cancers with long latencies, large geographic zones, and populations that reside at large distances from nuclear facilities are better suited for public relations than for scientific purposes

The mitochondrial DNA T16189C polymorphism and HIV-associated cardiomyopathy: a genotype-phenotype association study

<p>Abstract</p> <p>Background</p> <p>The mitochondrial DNA (mtDNA) T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV).</p> <p>Methods</p> <p>A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection) were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer.</p> <p>Results</p> <p>The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93), gender (males 60% vs 53%, P = 0.54), and stage of HIV disease (mean CD4 T cell count 260.7/μL vs. 176/μL, P = 0.21). The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30) in the HIV-associated cardiomyopathy cases and 13.5% (5/37) in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11).</p> <p>Conclusion</p> <p>The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.</p

Low cigarette consumption and risk of coronary heart disease and stroke: meta-analysis of 141 cohort studies in 55 study reports.

OBJECTIVE: To use the relation between cigarette consumption and cardiovascular disease to quantify the risk of coronary heart disease and stroke for light smoking (one to five cigarettes/day). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline 1946 to May 2015, with manual searches of references. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective cohort studies with at least 50 events, reporting hazard ratios or relative risks (both hereafter referred to as relative risk) compared with never smokers or age specific incidence in relation to risk of coronary heart disease or stroke. DATA EXTRACTION/SYNTHESIS: MOOSE guidelines were followed. For each study, the relative risk was estimated for smoking one, five, or 20 cigarettes per day by using regression modelling between risk and cigarette consumption. Relative risks were adjusted for at least age and often additional confounders. The main measure was the excess relative risk for smoking one cigarette per day (RR1_per_day-1) expressed as a proportion of that for smoking 20 cigarettes per day (RR20_per_day-1), expected to be about 5% assuming a linear relation between risk and consumption (as seen with lung cancer). The relative risks for one, five, and 20 cigarettes per day were also pooled across all studies in a random effects meta-analysis. Separate analyses were done for each combination of sex and disorder. RESULTS: The meta-analysis included 55 publications containing 141 cohort studies. Among men, the pooled relative risk for coronary heart disease was 1.48 for smoking one cigarette per day and 2.04 for 20 cigarettes per day, using all studies, but 1.74 and 2.27 among studies in which the relative risk had been adjusted for multiple confounders. Among women, the pooled relative risks were 1.57 and 2.84 for one and 20 cigarettes per day (or 2.19 and 3.95 using relative risks adjusted for multiple factors). Men who smoked one cigarette per day had 46% of the excess relative risk for smoking 20 cigarettes per day (53% using relative risks adjusted for multiple factors), and women had 31% of the excess risk (38% using relative risks adjusted for multiple factors). For stroke, the pooled relative risks for men were 1.25 and 1.64 for smoking one or 20 cigarettes per day (1.30 and 1.56 using relative risks adjusted for multiple factors). In women, the pooled relative risks were 1.31 and 2.16 for smoking one or 20 cigarettes per day (1.46 and 2.42 using relative risks adjusted for multiple factors). The excess risk for stroke associated with one cigarette per day (in relation to 20 cigarettes per day) was 41% for men and 34% for women (or 64% and 36% using relative risks adjusted for multiple factors). Relative risks were generally higher among women than men. CONCLUSIONS: Smoking only about one cigarette per day carries a risk of developing coronary heart disease and stroke much greater than expected: around half that for people who smoke 20 per day. No safe level of smoking exists for cardiovascular disease. Smokers should aim to quit instead of cutting down to significantly reduce their risk of these two common major disorders.This study was supported by a core grant from Cancer Research UK (C444/A15953)

Is standard breast-conserving therapy (BCT) in elderly breast cancer patients justified? A prospective measurement of acute toxicity according CTC-classification

<p>Abstract</p> <p>Background</p> <p>Breast conserving therapy (BCT) is an accepted treatment for early-stage breast cancer. This study aimed to measure prospectively acute radiation-related toxicity and to create a comprehensive data base for long-term temporal analyses of 3D conformal adjuvant radiotherapy. The specific aspect of age has been neglected by traditional research. Therefore, the impact of age on acute BCT toxicity should be also specifically adressed.</p> <p>Methods</p> <p>Toxicity was measured in 109 patients at initiation (t1), during radiotherapy (t2-t7), and 6 weeks after treatment completion (t8) using a new topographic module. Organ systems were recorded in 15 scales and scored according to symptom intensity (grade 0-5) based on CTC (Common Toxicity Criteria) -classification. Radiotherapy was virtually CT-based planned and applied with 6-MeV-photons. Mean total dose was 60.1 Gy. Patients were stratified by age in 3 Groups: <50, 50-60, and >60 years.</p> <p>Results</p> <p>Registered toxicity was generally low. Mean overall-grade climbed from 0.29-0.40 (t1-t7), and dropped to 0.23 (t8). Univariate analyses revealed slightly higher toxicity in older (> 60 years) versus young patients (< 50 years) in 2 scales only: breast-symmetry (p = 0.033), and arm function (p = 0.007). However, in the scale "appetite" toxicity was higher in younger (< 50 years) versus older (> 60 years) patients (p = 0.039). Toxicity differences in all other scales were not significant. Between older (> 60 years) and midaged patients (50-60 years) no significant differences in toxicity were found. This was also true for the comparison between young (< 50 years) versus midaged patient groups (50-60 years).</p> <p>Conclusion</p> <p>The treatment concept of BCT for breast cancer is generally well tolerated. The toxicity-measurement with the new topographic module is feasible. Not modified standard treatment for BC should be performed in elderly women.</p