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1
Chalupka, Stephanie. "Selective Estrogen Modulators for the Primary Prevention of Breast Cancer." AAOHN Journal 59, no. 1 (January 1, 2011): 48. http://dx.doi.org/10.3928/08910162-20101228-04.
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Chalupka, Stephanie. "Selective Estrogen Modulators for the Primary Prevention of Breast Cancer." AAOHN Journal 59, no. 1 (January 2011): 48. http://dx.doi.org/10.1177/216507991105900106.
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Chalupka, Stephanie. "Selective Estrogen Modulators for the Primary Prevention of Breast Cancer." AAOHN Journal 59, no. 1 (January 2011): 48. http://dx.doi.org/10.1177/216507991105900107.
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Fabian, Carol J., and Bruce F. Kimler. "Selective Estrogen-Receptor Modulators for Primary Prevention of Breast Cancer." Journal of Clinical Oncology 23, no. 8 (March 10, 2005): 1644–55. http://dx.doi.org/10.1200/jco.2005.11.005.
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Mishra, Nalini, Lalitha Priya Nekkanti, Poulami Barma, Ishan Mishra, and Ishan Mishra. "Adjunctive misoprostol for prevention of post-partum haemorrhage: a pragmatic strategy of selective sequential administration." International Journal of Reproduction, Contraception, Obstetrics and Gynecology 10, no. 2 (January 28, 2021): 669. http://dx.doi.org/10.18203/2320-1770.ijrcog20210325.
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Background: To evaluate the effect of adjunctive misoprostol in preventing postpartum haemorrhage (PPH) by selective administration above threshold bleeding in order to reduce its side effects in comparison with primary prevention with oxytocin alone.Methods: It was a prospective observational cohort study conducted at Government medical College of central India. Population included 500 low risk women delivering vaginally. After having received oxytocin as primary prevention, women were monitored for bleeding by quantitative assessment of blood loss (QBL) using an innovative drape (kept prepared at the point of care) and once bleeding crossed 350 ml mark, alternate women were given 800 µg misoprostol sublingually as an adjuvant (study group) and compared with those who did not receive adjuvant misoprostol (control group). Main outcome measure: Comparing the incidence of PPH and side effects between study and control group.Results: 150 women had blood loss >350 ml which constituted 76 women in study and control group each. Incidence of PPH was significantly less in the study group (10.52 versus 22.36%, p<0.05, RR 0.470 95% CI= 0.216-1.024). Though side effects were more (38.15%) in study group but these were mild in nature and when the number was extrapolated to all recruited women, the incidence came down to 11.6%.Conclusions: Sequential adjuvant misoprostol at 350 ml blood loss after primary prevention with oxytocin is an effective and pragmatic strategy for preventing PPH when compared to oxytocin alone but with reduced overall side effects owing to less number of women receiving misoprostol.
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Rees, Margaret, and John Stevenson. "Primary prevention of coronary heart disease in women." Menopause International 14, no. 1 (March 2008): 40–45. http://dx.doi.org/10.1258/mi.2007.007037.
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The British Menopause Society Council is committed to provide up-to-date authoritative reviews to aid health professionals to inform and advise women about key issues in post reproductive health. Coronary heart disease (CHD) is a leading cause of death in women. Observational studies have consistently shown estrogen to help prevent CHD in postmenopausal women. The large randomized controlled Women's Health Initiative (WHI) trial did not confirm these observational findings. However, further analyses of the WHI study as well as the observational Nurses’ Health Study have now found that the timing of onset of hormone replacement therapy (HRT) use is important and that estrogen may have a protective role in CHD in women aged 50–59 years. This consensus statement will examine the evidence regarding HRT and non-estrogen therapies (lipid lowering agents, aspirin, antihypertensives, antidiabetic medications, selective estrogen receptor modulators [SERMs]) as well as diet, lifestyle and smoking cessation in the primary prevention of CHD in women.
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BALTĂ, Mihaela Daniela, Mihaela Adela IANCU, and Dumitru MATEI. "NEW APPROACHES TO OSTEOPOROSIS IN PRIMARY CARE." Romanian Journal of Medical Practice 12, no. 4 (December 31, 2017): 184–91. http://dx.doi.org/10.37897/rjmp.2017.4.2.
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Osteoporosis is a disease that affects an increasing number of people, given the tendency of aging populations. Fragile bone and increases risk of bones breaking, their consequences, impairment of quality of life have prompted health policies to provide a greater insight into this condition. It is important to identify the risk factors and start the preventive and curative treatment as early as possible. Current guidelines recommend using the FRAX score to determine the risk of major fracture over the next 10 years, followed by DXA determination. The current guidelines highlight the importance of non-medication measures, calcium and vitamin D intake. Among the therapeutic agents used in the treatment of osteoporosis, the first line are bisphosphonates poor, in case of intolerance, bisphosphonates iv or antibodies anti RANKL (denosumab). Selective estrogen receptor modulators and hormone replacement therapy are not routinely indicated, and recombinant PTH is expensive and is intended for severe and resistant forms. The adherence to treatment is poor, so we need measures to increase prevention, screening and early treatment of osteoporosis, as well as measures to educate the population.
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Minder, C. Michael. "Making the Case for Selective Use of Statins in the Primary Prevention Setting." Archives of Internal Medicine 171, no. 17 (September 26, 2011): 1593. http://dx.doi.org/10.1001/archinternmed.2011.349.
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Teesson, M., N. C. Newton, T. Slade, N. Carragher, E. L. Barrett, K. E. Champion, E. V. Kelly, N. K. Nair, L. A. Stapinski, and P. J. Conrod. "Combined universal and selective prevention for adolescent alcohol use: a cluster randomized controlled trial." Psychological Medicine 47, no. 10 (February 22, 2017): 1761–70. http://dx.doi.org/10.1017/s0033291717000198.
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BackgroundNo existing models of alcohol prevention concurrently adopt universal and selective approaches. This study aims to evaluate the first combined universal and selective approach to alcohol prevention.MethodA total of 26 Australian schools with 2190 students (mean age: 13.3 years) were randomized to receive: universal prevention (Climate Schools); selective prevention (Preventure); combined prevention (Climate Schools and Preventure; CAP); or health education as usual (control). Primary outcomes were alcohol use, binge drinking and alcohol-related harms at 6, 12 and 24 months.ResultsClimate, Preventure and CAP students demonstrated significantly lower growth in their likelihood to drink and binge drink, relative to controls over 24 months. Preventure students displayed significantly lower growth in their likelihood to experience alcohol harms, relative to controls. While adolescents in both the CAP and Climate groups demonstrated slower growth in drinking compared with adolescents in the control group over the 2-year study period, CAP adolescents demonstrated faster growth in drinking compared with Climate adolescents.ConclusionsFindings support universal, selective and combined approaches to alcohol prevention. Particularly novel are the findings of no advantage of the combined approach over universal or selective prevention alone.
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Baldwin, Robert C. "Preventing late-life depression: a clinical update." International Psychogeriatrics 22, no. 8 (July 1, 2010): 1216–24. http://dx.doi.org/10.1017/s1041610210000864.
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ABSTRACTBackground: Achieving remission in late-life depressive disorder is difficult; it is far better to prevent depression. In the last ten years there have been a number of clinical studies of the feasibility of prevention.Methods: A limited literature review was undertaken of studies from 2000 specifically concerning the primary prevention of late-life depressive disorder or where primary prevention is a relevant secondary outcome.Results: Selective primary prevention (targeting individuals at risk but not expressing depression) has been shown to be effective for stroke and macular degeneration but not hip fracture. It may also prove effective for the depression associated with caregiving in dementia. Emerging evidence finds effectiveness for indicated prevention (in those identified with subthreshold depression often with other risk factors such as functional limitation). Despite a number of promising risk factors (for example, diet, exercise, vascular risk factors, homocysteine and insomnia), universal prevention of late-life depression (acting to reduce the impact of risk factors at the population level) has no current evidence base, although a population approach might mitigate suicide.Conclusion: Interventions which work in preventing late-life depression include antidepressant medication in standard doses and Problem-Solving Treatment. When integrated into a care model, such as collaborative care, prevention is feasible but more economic studies are needed.
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Lionis, Christos, Marilena Anastasaki, Antonios Bertsias, Agapi Angelaki, Axel C. Carlsson, Hrafnhildur Gudjonsdottir, Per Wändell, et al. "High Variability in Implementation of Selective-Prevention Services for Cardiometabolic Diseases in Five European Primary Care Settings." International Journal of Environmental Research and Public Health 17, no. 23 (December 4, 2020): 9080. http://dx.doi.org/10.3390/ijerph17239080.
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(1) Background: Cardiometabolic diseases are the most common cause of death worldwide. As part of a collaborative European study, this paper aims to explore the implementation of primary care selective-prevention services in five European countries. We assessed the implementation process of the selective-prevention services, participants’ cardiometabolic profile and risk and participants’ evaluation of the services, in terms of feasibility and impact in promoting a healthy lifestyle. (2) Methods: Eligible participants were primary care patients, 40–65 years of age, without any diagnosis of cardiometabolic disease. Two hundred patients were invited to participate per country. The extent to which participants adopted and completed the implementation of selective-prevention services was recorded. Patient demographics, lifestyle-related cardiometabolic risk factors and opinions on the implementation’s feasibility were also collected. (3) Results: Acceptance rates varied from 19.5% (n = 39/200) in Sweden to 100% (n = 200/200) in the Czech Republic. Risk assessment completion rates ranged from 65.4% (n = 70/107) in Greece to 100% (n = 39/39) in Sweden. On a ten-point scale, the median (25–75% quartile) of participant-reported implementation feasibility ranged from 7.4 (6.9–7.8) in Greece to 9.2 (8.2–9.9) in Sweden. Willingness to change lifestyle exceeded 80% in all countries. (4) Conclusions: A substantial variation in the implementation of selective-prevention receptiveness and patient risk profile was observed among countries. Our findings suggest that the design and implementation of behavior change cardiometabolic programmes in each country should be informed by the local context and provide some background evidence towards this direction, which can be even more relevant during the current pandemic period.
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Robinson, Robert G., and Ricardo E. Jorge. "Prevention of first-episode depression: progress and potential." British Journal of Psychiatry 194, no. 4 (April 2009): 296–97. http://dx.doi.org/10.1192/bjp.bp.108.059873.
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SummaryPreventive intervention for first-episode depression is an exciting, emerging field. Many questions remain, however. Should we target patients who have sub-syndromal symptom elevations (i.e. indicated intervention) or should we intervene in high-risk groups (i.e. selective intervention)? Furthermore, should primary outcomes be incident depressions or long-term decreases in morbidity or mortality?
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Filion, Kristian B., Xuanqian Xie, Charlotte J. van der Avoort, Nandini Dendukuri, and James M. Brophy. "Microvolt T-wave alternans and the selective use of implantable cardioverter defibrillators for primary prevention: A cost-effectiveness study." International Journal of Technology Assessment in Health Care 25, no. 02 (March 31, 2009): 151–60. http://dx.doi.org/10.1017/s0266462309090205.
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Objectives:Implantable cardioverter defibrillators (ICDs) are an effective but expensive treatment for the prevention of sudden cardiac deaths in patients with severe left-ventricular dysfunction. Recent studies suggest that microvolt T-wave alternans (MTWA) predicts mortality and severe arrhythmic events in this population. However, the impact of MTWA on ICD cost-effectiveness is unknown.Methods:A Markov decision-analysis model evaluated three treatment strategies for primary prevention in patients with severe left-ventricular dysfunction: (i) medical therapy for all; (ii) ICD therapy for all; and (iii) selective ICD therapy based on non-negative (positive or indeterminate) MTWA test results. Incremental cost-effectiveness ratios (ICER) were calculated from the perspective of a third party payer using a 10-year time horizon. Sensitivity analyses examined the robustness of the estimates.Results:A treatment strategy involving ICD therapy in all patients was associated with an ICER of $121,800/quality-adjusted life-year (QALY) compared with medical therapy, whereas a treatment strategy involving the selective use of ICDs based on MTWA test results was associated with an ICER of $108,900/QALY compared with medical therapy. Sensitivity analyses suggest that, under most scenarios, the selective use of ICDs based on MTWA results does not decrease the ICER to below $100,000/QALY.Conclusion:MTWA only marginally improves the cost-effectiveness of ICDs for primary prevention in patients with severe left-ventricular dysfunction. There remains a need for improved means to effectively identify which patients will derive the greatest benefit from ICD implantation.
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Stevenson, John C. "BMS consensus statement for primary prevention of coronary heart disease in women." Post Reproductive Health 25, no. 2 (June 2019): 64–69. http://dx.doi.org/10.1177/2053369119852006.
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The British Menopause Society Council is committed to provide up to date authoritative reviews to aid health professionals to inform and advise women about key issues in postreproductive health. Coronary heart disease is a leading cause of death in women. Observational studies have consistently shown estrogen to help prevent coronary heart disease in postmenopausal women. The large randomized controlled Women’s Health Initiative trial initially did not confirm these observational findings. However, further analyses of the Women’s Health Initiative study as well as meta-analyses of randomized clinical trials of hormone replacement therapy and of the observational Nurses’ Health Study have now found that the timing of onset of hormone replacement therapy use is important and that estrogen may have an important protective role in coronary heart disease, particularly in women initiating treatment below age 60 years. This consensus statement will examine the evidence regarding hormone replacement therapy and non-estrogen therapies (lipid-lowering agents, aspirin, antihypertensives, anti-diabetic medications, selective estrogen receptor modulators) as well as diet, lifestyle and smoking cessation in the primary prevention of coronary heart disease in women.
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Дашацыренова, Дарима, Darima Dashatsyrenova, Альбина Гаврилова, Albina Gavrilova, Павел Твердохлебов, and Pavel Tverdokhlebov. "ESOPHAGEAL VARICEAL LIGATION IN THE PRIMARY AND SECONDARY PREVENTION OF VARICEAL BLEEDING." Acta biomedica scientifica 2, no. 5 (January 18, 2018): 151–53. http://dx.doi.org/10.12737/article_5a3a0ead02b258.50539404.
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This article is devoted to experience of endoscopic ligation of varices in N.A. Semashko Republic Clinical Hospital.
We analyzed the results of ligation in 28 patients treated since February 2013 to March 2016. Selected patients had
diagnoses of liver cirrhosis, syndrome of portal hypertension of different origin, 10 (35.5 %) had the history of one or
more episodes of bleeding from varicose veins of the esophagus. Endoscopic ligation was performed for patients with
varices of grade 3–4 according to J. Paquet classification, grade 3 according to N. Soehendra, K. Binmoeller classifica-
tion improving primary and secondary prevention of bleeding. The effectiveness of endoscopic ligation as a method
of primary and secondary prevention of bleeding from the varices, with subsequent transfer to oral administration of
non-selective β-adrenoblockers was evaluated. In the result of the study throughout the entire period of observation
we indicated no episodes of esophageal bleeding and established a low rate of recurrence of varices. Those patients
who, after the first endoscopic ligation session, followed the recommendations for taking beta-blockers, have a better
prognosis and the outcome in relation to patients who have neglected the recommendations. During the first year of
follow-up there was one fatal outcome – a man with VHC died as a result of hepatocellular insufficiency.
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Bonten, Tobias N., Sanne Marije Verkleij, Rianne MJJ van der Kleij, Karin Busch, Wilbert B. van den Hout, Niels H. Chavannes, and Mattijs E. Numans. "Selective prevention of cardiovascular disease using integrated lifestyle intervention in primary care: protocol of the Healthy Heart stepped-wedge trial." BMJ Open 11, no. 7 (July 2021): e043829. http://dx.doi.org/10.1136/bmjopen-2020-043829.
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IntroductionLifestyle interventions are shown to be effective in improving cardiovascular disease (CVD) risk factors. It has been suggested that general practitioners can play an essential role in CVD prevention. However, studies into lifestyle interventions for primary care patients at high cardiovascular risk are scarce and structural implementation of lifestyle interventions can be challenging. Therefore, this study aims to (1) evaluate (cost-)effectiveness of implementation of an integrated group-based lifestyle programme in primary care practices; (2) identify effective intervention elements and (3) identify implementation determinants of an integrated group-based lifestyle intervention for patients with high cardiovascular risk.Methods and analysisThe Healthy Heart study is a non-randomised cluster stepped-wedge trial. Primary care practices will first offer standard care during a control period of 2–6 months, after which practices will switch (step) to the intervention, offering participants a choice between a group-based lifestyle programme or standard care. Participants enrolled during the control period (standard care) will be compared with participants enrolled during the intervention period (combined standard care and group-based lifestyle intervention). We aim to include 1600 primary care patients with high cardiovascular risk from 55 primary care practices in the area of The Hague, the Netherlands. A mixed-methods process evaluation will be used to simultaneously assess effectiveness and implementation outcomes. The primary outcome measure will be achievement of individual lifestyle goals after 6 months. Secondary outcomes include lifestyle change of five lifestyle components (smoking, alcohol consumption, diet, weight and physical activity) and improvement of quality of life and self-efficacy. Outcomes are assessed using validated questionnaires at baseline and 3, 6, 12 and 24 months of follow-up. Routine care data will be used to compare blood pressure and cholesterol levels. Cost-effectiveness of the lifestyle intervention will be evaluated. Implementation outcomes will be assessed using the RE-AIM model, to assesses five dimensions of implementation at different levels of organisation: reach, efficacy, adoption, implementation and maintenance. Determinants of adoption and implementation will be assessed using focus groups consisting of professionals and patients.Ethics and disseminationThis study is approved by the Ethics Committee of the Leiden University Medical Center (P17.079). Results will be shared with the primary care group, healthcare providers and patients, and will be disseminated through journal publications and conference presentations.Trial registration numberNL60795.058.17. Status: pre-results
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Sonderlund, Anders Larrabee, Trine Thilsing, Joke Korevaar, Monika Hollander, Christos Lionis, Francois Schellevis, Per Wändell, et al. "An evidence-based toolbox for the design and implementation of selective-prevention primary-care initiatives targeting cardio-metabolic disease." Preventive Medicine Reports 16 (December 2019): 100979. http://dx.doi.org/10.1016/j.pmedr.2019.100979.
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Pimentel, R., C. Gregório, and P. Figueiredo. "Antibiotic prophylaxis for prevention of spontaneous bacterial peritonitis in liver cirrhosis: systematic review." Acta Gastro Enterologica Belgica 84, no. 2 (June 2021): 333–42. http://dx.doi.org/10.51821/84.2.333.
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Background and aim: Spontaneous bacterial peritonitis is a potentially life-threatening infection in patients with liver cirrhosis and ascites. Its prevention is vital to improve prognosis of cirrhotic patients. The main objective of this systematic review was to evaluate what is the most efficacious and safest antibiotic prophylactic strategy. Methods: Studies were located by searching PubMed and Cochrane Central Register of Controlled Trials in The Cochrane Library until February 2019. Randomized controlled trials evaluating primary or secondary spontaneous bacterial peritonitis prophylaxis in cirrhotic patients with ascites were included. The selection of studies was performed in two stages: screening of titles and abstracts, and assessment of the full papers identified as relevant, considering the inclusion criteria. Data were extracted in a standardized way and synthesized qualitatively. Results: Fourteen studies were included. This systematic review demonstrated that daily norfloxacin is effective as a prophylactic antibiotic for the prevention of spontaneous bacterial peritonitis in patients with cirrhosis. Once weekly ciprofloxacin was not inferior to once daily norfloxacin, with good tolerance and no induced resistance. Trimethoprim-sulfamethoxazole and norfloxacin have similar efficacy for primary and secondary prophylaxis of spontaneous bacterial peritonitis, however, trimethoprim-sulfamethoxazole was associated with an increased risk of developing an adverse event. Rifaximin was more effective than norfloxacin in the secondary prophylaxis of spontaneous bacterial peritonitis, with a significant decrease in adverse events and mortality rate. Conclusions: Continuous long-term selective intestinal decontamination with norfloxacin is the most widely used prophylactic strategy in spontaneous bacterial peritonitis, yet other equally effective and safe options are available.
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Crew, Katherine D. "Addressing Barriers to Uptake of Breast Cancer Chemoprevention for Patients and Providers." American Society of Clinical Oncology Educational Book, no. 35 (May 2015): e50-e58. http://dx.doi.org/10.14694/edbook_am.2015.35.e50.
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Breast cancer is the most common malignancy among women in the United States, and the primary prevention of this disease is a major public health issue. Because there are relatively few modifiable breast cancer risk factors, pharmacologic interventions with antiestrogens have the potential to significantly affect the primary prevention setting. Breast cancer chemoprevention with selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene, and with aromatase inhibitors (AIs) exemestane and anastrozole, is underutilized despite several randomized controlled trials demonstrating up to a 50% to 65% relative risk reduction in breast cancer incidence among women at high risk. An estimated 10 million women in the United States meet high-risk criteria for breast cancer and are potentially eligible for chemoprevention, but less than 5% of women at high risk who are offered antiestrogens for primary prevention agree to take it. Reasons for low chemoprevention uptake include lack of routine breast cancer risk assessment in primary care, inadequate time for counseling, insufficient knowledge about antiestrogens among patients and providers, and concerns about side effects. Interventions designed to increase chemoprevention uptake, such as decision aids and incorporating breast cancer risk assessment into clinical practice, have met with limited success. Clinicians can help women make informed decisions about chemoprevention by effectively communicating breast cancer risk and enhancing knowledge about the risks and benefits of antiestrogens. Widespread adoption of chemoprevention will require a major paradigm shift in clinical practice for primary care providers (PCPs). However, enhancing uptake and adherence to breast cancer chemoprevention holds promise for reducing the public health burden of this disease.
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Suryapranata, Harry, Massimo Chiariello, and Giuseppe De Luca. "Prevention of distal embolization in patients undergoing mechanical revascularization for acute myocardial infarction." Thrombosis and Haemostasis 96, no. 12 (2006): 700–710. http://dx.doi.org/10.1160/th06-06-0319.
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SummaryDistal embolization is a relatively common complication in primary angioplasty and is associated with poor perfusion and higher mortality. The aim of this article is to critically review literature on pharmacological and mechanical therapies to prevent distal embolization in patients undergoing primary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE, Pubmed) from January 1990 to March 2006 and scientific session abstracts (from January 1990 to March 2006) and oral presentation and/or expert slide presentations (from January 2002 to March 2006) (on TCT, AHA, ESC, ACC and EuroPCR websites). No language restrictions were enforced. Several pharmacological and mechanical therapies have been investigated to prevent distal embolization.Abciximab has been shown to reduce mortality,and its early admin-istration may provide additional benefits in outcome due to improvement in preprocedural reperfusion.The results of randomized trials on adjunctive mechanical devices remain controversial. Even though they reduce distal embolization and improve myocardial perfusion, no benefits have been observed in terms of 30-day survival. Adjunctive abciximab has improved survival, and its early administration is to be recommended, particularly when transportation to a primary PCI center is needed. Pending the results of large randomized trials with long-term follow-up data, the routine use of adjunctive mechanical devices to prevent distal embolization cannot be recommended, though selective use of these devices might be considered when large thrombotic burden is present.
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Král, Norbert, Anne-Karien M. de Waard, François G. Schellevis, Joke C. Korevaar, Christos Lionis, Axel C. Carlsson, Anders Larrabee Sønderlund, et al. "What should selective cardiometabolic prevention programmes in European primary care look like? A consensus-based design by the SPIMEU group." European Journal of General Practice 25, no. 3 (July 3, 2019): 101–8. http://dx.doi.org/10.1080/13814788.2019.1641195.
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Garbuzenko, Dmitry V. "Principles of primary prophylaxis of bleeding from oesophagealvaricies in patients with liver cirrhosis." Clinical Medicine (Russian Journal) 94, no. 7 (September 7, 2016): 503–9. http://dx.doi.org/10.18821/0023-2149-2016-94-7-503-509.
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The principles of primary prevention of bleeding from esophageal varices in patients with liver cirrhosis are discussed with reference to the stage ofportal hypertension. The information was collectedfrom the PubMed database, Google Scholar retrieval system, Cochrane reviews, and lists of references from relevant publications for 1980-2015 using the key words «bleeding from esophageal varices», «prophylaxis», «portal hypertension». Inclusion criteria were confined to primary prophylaxis of bleeding from esophageal varices in patients with liver cirrhosis. The analysis showed that the drugs of choice for primary prophylaxis of bleeding from esophageal varices in patients with liver cirrhosis are non-selective beta-adrenoblockers, but their application is indicated only in case of clinicallyl significant portal hypertension in patients with large and mediumsize esophageal varices. When the use of these drugs is contraindicated, endoscopic ligation of esophageal varices can be recommended.
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Cazzaniga, Massimiliano, Clara Varricchio, Chiara Montefrancesco, Irene Feroce, and Aliana Guerrieri-Gonzaga. "Fenretinide (4-HPR): A Preventive Chance for Women at Genetic and Familial Risk?" Journal of Biomedicine and Biotechnology 2012 (2012): 1–9. http://dx.doi.org/10.1155/2012/172897.
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The incidence and mortality of breast cancer have been recently influenced by several new therapeutic strategies. In particular our knowledge on cancer precursors, risk biomarkers, and genetics has considerably increased, and prevention strategies are being successfully explored. Since their discovery, retinoids, the natural and synthetic derivatives of vitamin A, have been known to play a crucial role in cell and tissue differentiation and their ability to inhibit carcinogenesis has made them the ideal chemopreventive agents studied in several preclinical and clinical trials. Fenretinide (4-HPR) is the most studied retinoid in breast cancer chemoprevention clinical trials due to its selective accumulation in breast tissue and its favorable toxicological profile. This agent showed a significative reduction of the incidence of second breast tumors in premenopausal women confirmed after 15-year followups. Considering Fenretinide protective action, a similar trend on ovarian cancer, this drug warrants reevaluations as a preventive agent for high-risk young women, such as BRCA-1 and 2 mutation carriers or with a high familial risk. This favorable effect therefore provides a strong rationale for a primary prevention trial in these unaffected cohort of women.
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Sasaki, Clarence T., Jagdeep S. Hundal, and Young-Ho Kim. "Protective Glottic Closure: Biomechanical Effects of Selective Laryngeal Denervation." Annals of Otology, Rhinology & Laryngology 114, no. 4 (April 2005): 271–75. http://dx.doi.org/10.1177/000348940511400404.
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Glottic closure constitutes the primary mechanism for prevention of intradeglutitive and postdeglutitive aspiration. Laryngeal paralysis therefore exerts a considerable impact on deglutition, yet little is understood regarding the biomechanical effects of selective denervation on the laryngeal protective function. We measured the glottic closing force (GCF) in each of 6 male, 40-kg Yorkshire pigs 1) after selective unilateral superior laryngeal nerve (SLN) section; 2) after selective unilateral recurrent laryngeal nerve (RLN) section; and/or 3) after combined SLN-RLN section as both right and left SLNs were simultaneously stimulated to evoke the glottic closure response. Stimulation was provided through an oscilloscope with bipolar platinum-iridium electrodes, and the GCF was measured with a pressure transducer positioned between the vocal cords. Six repetitive measures of GCF were obtained before nerve section, and 6 after nerve section, in each subject. Unilateral SLN section reduced the GCF to 54.14% of control, RLN section reduced the GCF to 23.39% of control, and combined SLN-RLN section reduced the GCF to 22.67% of control. These findings underscore the profound differential effects exerted by isolated lesions on the glottic closure function.
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Ito, Kouta, Victoria S. Blinder, and Elena B. Elkin. "Cost Effectiveness of Fracture Prevention in Postmenopausal Women Who Receive Aromatase Inhibitors for Early Breast Cancer." Journal of Clinical Oncology 30, no. 13 (May 1, 2012): 1468–75. http://dx.doi.org/10.1200/jco.2011.38.7001.
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Purpose Aromatase inhibitors (AIs) increase the risk of osteoporosis and related fractures in postmenopausal women who receive adjuvant AIs for hormone receptor (HR) –positive early breast cancer (EBC). We compared the cost effectiveness of alternative screening and treatment strategies for fracture prevention. Methods We developed a Markov state transition model to simulate clinical practice and outcomes in a hypothetical cohort of women age 60 years with HR-positive EBC starting a 5-year course of AI therapy after primary surgery for breast cancer. Outcomes were quality-adjusted life-years (QALYs), lifetime cost, and incremental cost-effectiveness ratio (ICER). We compared the following strategies: no intervention; one-time bone mineral density (BMD) screening and selective bisphosphonate therapy in women with osteoporosis or osteopenia; annual BMD screening and selective bisphosphonate therapy in women with osteoporosis or osteopenia; and universal bisphosphonate therapy. Results ICERs for annual BMD screening followed by oral bisphosphonates for those with osteoporosis, annual BMD screening followed by oral bisphosphonates for those with osteopenia, and universal treatment with oral bisphosphonates were $87,300, $129,300, and $283,600 per QALY gained, respectively. One-time BMD screening followed by oral bisphosphonates for those with osteoporosis or osteopenia was dominated. Our results were sensitive to age at the initiation of AI therapy, type of bisphosphonates, post-treatment residual effect of bisphosphonates, and a potential adjuvant benefit of intravenous bisphosphonates. Conclusion In postmenopausal women receiving adjuvant AIs for HR-positive EBC, a policy of baseline and annual BMD screening followed by selective treatment with oral bisphosphonates for those diagnosed with osteoporosis is a cost-effective use of societal resources.
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Bhugra, D. "EPA Guidance on Prevention of Mental Illness and Promotion of Mental Health." European Psychiatry 26, S2 (March 2011): 2199. http://dx.doi.org/10.1016/s0924-9338(11)73902-5.
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Prevention of mental illness and promotion of mental health are a significant component of any clinician's clinical work load. However, often this aspect is omitted from training and service delivery due to insufficient resources and the sheer volume of clinical load. Considerable evidence confirms that prevention can significantly reduce the onset of and subsequent related burdens to mental illness, and associated personal, social and economic costs. Often prevention and promotion get confused, and further mental illness and mental health are related but distinct dimensions. Acute mental illness usually prevents positive mental health or wellbeing, yet similarly someone without mental illness can have poor mental health and poor well being. Prevention of mental illness relates closely to and can result from promotion of mental health and associated resilience.Prevention can be categorised in multiple ways and most clinicians regularly utilise secondary and tertiary prevention. Primary prevention addresses wider determinants across whole populations. Selective prevention targets groups at higher risk of developing disorder. Secondary prevention involves early detection and intervention and corresponds to indicated prevention. This lecture summarises these challenges and the impact of mental illness, and develops the case for prevention. The risk and protective factors for mental illness and various ages of onset are presented. Interventions at different life stages are also outlined. The lecture relies on the EPA Guidance on prevention of mental ill health and promotion of mental well being using the development of UK policy as structure. Future steps will be presented within European and global context.
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Luis-Joaquin, Garcia-Lopez, Espinosa-Fernández Lourdes, and Muela-Martínez José A. "Behavioral Inhibition in Childhood as A Risk Factor for Development of Social Anxiety Disorder: A Longitudinal Study." International Journal of Environmental Research and Public Health 17, no. 11 (June 2, 2020): 3941. http://dx.doi.org/10.3390/ijerph17113941.
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Previous research has suggested the association between behavioral inhibition (BI) and the development of social anxiety disorder in childhood. However, there is scarce research using longitudinal methodology in Spanish-speaking populations. To cover this gap, the sample comprised 73 children ranging from six to eight years who had been examined for BI two years earlier in home and school settings. Children and their parents were administered the Anxiety Disorders Interview Schedule for DSM-5-Child and Parent Versions to assess the presence of possible anxiety disorders. The results revealed the stability of BI symptomatology over time. Data also showed that BI children were almost ten times more likely to develop social anxiety disorder two years later, compared to no-BI children. As a result, findings suggest behavioral inhibition strongly predicts social anxiety disorder, making BI a logical focus for selective preventive interventions. Therefore, screening for behavioral inhibition holds promise for primary prevention.
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Jang, Ho-Jun, Jon Suh, Sung Woo Kwon, Sang-Don Park, Pyung Chun Oh, Jeonggeun Moon, Kyounghoon Lee, et al. "The selection of β-blocker after successful reperfusion in patients with ST-elevation myocardial infarction." Perfusion 35, no. 4 (October 14, 2019): 338–47. http://dx.doi.org/10.1177/0267659119878396.
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Background: The selection of β-blocker for survivors after primary intervention due to acute ST-elevation myocardial infarction seems crucial to improve the outcomes. However, rare comparison data existed for these patients. We aimed to compare the effectiveness of selective β-blockers to that of carvedilol in patients treated with primary intervention. Methods and results: Among the 1,485 patients in the “INTERSTELLAR” registry between 2007 and 2015, 238 patients with selective β-blockers (bisoprolol, nebivolol, atenolol, bevantolol, and betaxolol) and 988 with carvedilol were included and their clinical outcomes were compared for a 2-year observation period. In the clinical baseline characteristics, the unfavorable trends in the carvedilol group were high Killip presentation, lower ejection fractions, smaller diameters, and longer lengths of deployed stents. Although mortality (2.5% vs. 1.7%; p = 0.414) and the rate of stroke (0.8% vs. 0.6%; p = 0.693) were not different between groups, the rate of recurrent myocardial infarction (4.6% vs. 1.2%; p = 0.001) and of target vessel revascularization (4.2% vs. 0.9%; p < 0.001) were lower in the carvedilol group. After eliminating the difference by propensity matching, the similar outcome result was shown (all-cause death, 0.6% vs. 1.0%, p = 0.678; stroke, 0.6% vs. 1.2%, p = 0.479; myocardial infarction, 5.0% vs. 1.2%, p = 0.003; target vessel revascularization, 4.5% vs. 0.7%, p < 0.006) for 595 matched populations. The use of carvedilol was also determined to be an independent predictor for recurrent myocardial infarctions (hazard ratio = 0.305; p = 0.005; 95% confidence interval = 0.13-0.69). Conclusion: Use of a carvedilol in ST-segment myocardial infarction survivor is associated with lower recurrent myocardial infarction events. Thus, it might be the better choice of β-blocker for secondary prevention in ST-elevation myocardial infarction patients treated with primary percutaneous coronary intervention.
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Pinto, Rafael Zambelli, Mark R. Elkins, Anne M. Moseley, Catherine Sherrington, Robert D. Herbert, Christopher G. Maher, Paulo H. Ferreira, and Manuela L. Ferreira. "Many Randomized Trials of Physical Therapy Interventions Are Not Adequately Registered: A Survey of 200 Published Trials." Physical Therapy 93, no. 3 (March 1, 2013): 299–309. http://dx.doi.org/10.2522/ptj.20120206.
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BackgroundClinical trial registration has several putative benefits: prevention of selective reporting, avoidance of duplication, encouragement of participation, and facilitation of reviews. Previous surveys suggest that most trials are registered. However, these surveys examined only trials in journals with high impact factors, which may bias the results.PurposeThis study examined the completeness of clinical trial registration and the extent of selective reporting of outcomes in a random sample of published randomized trials in physical therapy.Data SourcesThis was a retrospective cohort study in which 200 randomized trials of physical therapy interventions were randomly selected from those published in 2009 and indexed in the Physiotherapy Evidence Database (PEDro), regardless of the publishing journal.Data ExtractionEvidence of registration was sought for each trial in the study, on clinical trial registers, and by contacting authors.Data SynthesisThe proportion of randomized trials that were registered was 67/200 (34%). This proportion was significantly lower than among the trials in journals with high impact factors, where the proportion was 75% (odds ratio=7.4, 95% confidence interval=2.6–21.4). Unambiguous primary outcomes (ie, method and time points of measurement clearly defined in the trial registry entry) were registered for 32 trials, and registration was adequate (ie, prospective with unambiguous primary outcomes) for 5/200 (2.5%) trials. Selective outcome reporting occurred in 23 (47%) of the 49 trials in which selective reporting was assessable.LimitationsThe inclusion of only English-language trials prevents generalization of the results to non–English-language trials.ConclusionsRegistration of randomized trials of physical therapy interventions is rarely adequate. Consequently, the putative benefits of registration are not being fully realized.
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Verdura, Sara, Elisabet Cuyàs, Verónica Ruiz-Torres, Vicente Micol, Jorge Joven, Joaquim Bosch-Barrera, and Javier A. Menendez. "Lung Cancer Management with Silibinin: A Historical and Translational Perspective." Pharmaceuticals 14, no. 6 (June 11, 2021): 559. http://dx.doi.org/10.3390/ph14060559.
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The flavonolignan silibinin, the major bioactive component of the silymarin extract of Silybum marianum (milk thistle) seeds, is gaining traction as a novel anti-cancer therapeutic. Here, we review the historical developments that have laid the groundwork for the evaluation of silibinin as a chemopreventive and therapeutic agent in human lung cancer, including translational insights into its mechanism of action to control the aggressive behavior of lung carcinoma subtypes prone to metastasis. First, we summarize the evidence from chemically induced primary lung tumors supporting a role for silibinin in lung cancer prevention. Second, we reassess the preclinical and clinical evidence on the effectiveness of silibinin against drug resistance and brain metastasis traits of lung carcinomas. Third, we revisit the transcription factor STAT3 as a central tumor-cell intrinsic and microenvironmental target of silibinin in primary lung tumors and brain metastasis. Finally, by unraveling the selective vulnerability of silibinin-treated tumor cells to drugs using CRISPR-based chemosensitivity screenings (e.g., the hexosamine biosynthesis pathway inhibitor azaserine), we illustrate how the therapeutic use of silibinin against targetable weaknesses might be capitalized in specific lung cancer subtypes (e.g., KRAS/STK11 co-mutant tumors). Forthcoming studies should take up the challenge of developing silibinin and/or next-generation silibinin derivatives as novel lung cancer-preventive and therapeutic biomolecules.
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Høivik, Hans Olav, Bart E. Laurijssens, Lutz O. Harnisch, Colleen K. Twomey, Ruth M. Dixon, Andrew JT Kirkham, Pauline M. Williams, Alison L. Wentz, and Martin W. Lunnon. "Lack of efficacy of the selective iNOS inhibitor GW274150 in prophylaxis of migraine headache." Cephalalgia 30, no. 12 (May 12, 2010): 1458–67. http://dx.doi.org/10.1177/0333102410370875.
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Introduction: This study investigated the efficacy and tolerability of the highly selective iNOS inhibitor GW274150 in prophylaxis of migraine headache. Subjects and methods: The study was conducted in two parts, each comprising a 4-week baseline period, a 12-week, double-blind, parallel-group treatment period, and a 4-week follow-up period. The study had an adaptive design in that findings of Part 1 of the study were used to inform the conduct of Part 2. Following an interim analysis at the end of Part 1, the trial could be stopped for futility or continued in Part 2 to study the full-dose response or to increase sample size in case initial assumptions had been violated. The primary end-point in both parts of the study was the probability of the occurrence of a migraine headache day during the baseline period and the treatment period. Results: In Part 1, adult male and female patients with migraine received GW274150 60 mg ( n = 37), 120 mg ( n = 37), or placebo ( n = 38) once daily for 12 weeks. In Part 2, female patients with migraine received GW274150 60 mg ( n = 160) or placebo ( n = 154) once daily for 12 weeks. GW274150 was no more effective than placebo for the primary efficacy end-point or any secondary efficacy end-point in Part 1 or Part 2. GW274150 was generally well tolerated. Conclusions: GW274150 at doses predicted to inhibit iNOS >80% did not differ from placebo in the prophylaxis of migraine. The results do not support a role of iNOS inhibition in migraine prevention.
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Wang, Jiping, Nancy L. Cho, Ann G. Zauber, Meier Hsu, Dawn Dawson, Amitabh Srivastava, Kisha Mitchell-Richards, Sanford D. Markowitz, and Monica M. Bertagnolli. "Expression of COX-2 and 15-PGDH in adenomas removed during pretreatment colonoscopy to predict chemopreventive efficacy of the selective COX-2 inhibitor, celecoxib." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 524. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.524.
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524 Background: The APC trial showed that patients at high risk for colorectal adenoma development experienced a 33-45% reduction in post-polypectomy adenoma detection when treated with the selective cyclooxygenase-2 (cox-2) inhibitor, celecoxib. Unfortunately, this study also found a small increased risk of cardiovascular toxicity among celecoxib users, preventing broad use of this agent for chemoprevention. Celecoxib inhibits expression of prostaglandin E2 (PGE2), an inflammatory mediator produced by fatty acid metabolism via cyclooxygenases, and degraded through the activity of 15-prostaglandin dehydrogenase (15-PGDH). Methods: Adenomas collected from APC trial participants prior to treatment were examined using immunohistochemistry (IHC) to assess expression of cox-2 (high vs. low) and 15-PGDH (present vs. absent). A combined variable to estimate tumor PGE2 levels identified cases as PGE2 low (Cox-2 low/15-PGDH present) or PGE2 high (Cox-2 high/15-PGDH present; Cox-2 high/15-PGDH absent; or Cox-2 low/15-PGDH absent). Mantel–Cox test was used to evaluate whether markers of PGE2 expression in these adenomas predicted benefit from celecoxib treatment for the primary study outcome of adenoma detection. Results: Biomarker determinations were achieved for 1295 cases, or 71% of patients with available outcome data. Patients whose baseline adenomas demonstrated elevated Cox-2 achieved the greatest overall reduction in adenoma risk with celecoxib treatment (RR 0.37; p = 0.0001). This risk reduction was less significant in the low Cox-2 category (RR 0.64). Patients with low estimated tumor PGE2 did not benefit from celecoxib for adenoma prevention (RR 0.95; p = 0.83). This is compared to a 41% reduction in adenoma detection with celecoxib treatment for patients in the high PGE2 category (RR 0.59; p < 0.0001). Conclusions: IHC to determine expression of target enzymes in pre-malignant adenomas provides significant prognostic and predictive information in patients treated with celecoxib for prevention of colorectal adenomas.
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Arango, Belisario A., Aurelio B. Castrellon, Edgardo S. Santos, and Stefan Gluck. "A Review of the Prevention of Invasive Breast Cancer with Raloxifene in Postmenopausal Women." Clinical Medicine. Therapeutics 1 (January 2009): CMT.S2063. http://dx.doi.org/10.4137/cmt.s2063.
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Breast cancer remains the second leading cause of malignancy-related death in women in the United States, regardless of advances in novel therapeutic agents. High priority should be emphasized in research aimed at the study of pharmacological and natural compounds that may potentially prevent the development of breast cancer in susceptible patients. Among the known selective estrogen receptor modulators with proven chemopreventive effects, raloxifene has been studied in a number of clinical trials evaluating this drug for the prevention of osteoporosis and coronary heart disease. The MORE and CORE trials had as a primary end point the efficacy of raloxifene in the treatment of women with osteoporosis. These studies showed that raloxifene reduced the risk of invasive breast cancer in postmenopausal women. However, the STAR trial showed no significant difference between raloxifene and tamoxifen recipients in the incidence of invasive breast cancer in postmenopausal women at high risk of invasive breast cancer. This review focuses on the chemopreventive properties of raloxifene and the clinical trials that have proven its efficacy as a chemopreventive agent in invasive breast cancer.
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Wald, I., E. Fruchter, K. Ginat, E. Stolin, D. Dagan, P. D. Bliese, P. J. Quartana, M. L. Sipos, D. S. Pine, and Y. Bar-Haim. "Selective prevention of combat-related post-traumatic stress disorder using attention bias modification training: a randomized controlled trial." Psychological Medicine 46, no. 12 (July 5, 2016): 2627–36. http://dx.doi.org/10.1017/s0033291716000945.
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BackgroundEfficacy of pre-trauma prevention for post-traumatic stress disorder (PTSD) has not yet been established in a randomized controlled trial. Attention bias modification training (ABMT), a computerized intervention, is thought to mitigate stress-related symptoms by targeting disruptions in threat monitoring. We examined the efficacy of ABMT delivered before combat in mitigating risk for PTSD following combat.MethodWe conducted a double-blind, four-arm randomized controlled trial of 719 infantry soldiers to compare the efficacy of eight sessions of ABMT (n = 179), four sessions of ABMT (n = 184), four sessions of attention control training (ACT; n = 180), or no-training control (n = 176). Outcome symptoms were measured at baseline, 6-month follow-up, 10 days following combat exposure, and 4 months following combat. Primary outcome was PTSD prevalence 4 months post-combat determined in a clinical interview using the Clinician-Administered PTSD Scale. Secondary outcomes were self-reported PTSD and depression symptoms, collected at all four assessments.ResultsPTSD prevalence 4 months post-combat was 7.8% in the no-training control group, 6.7% with eight-session ABMT, 2.6% with four-session ABMT, and 5% with ACT. Four sessions of ABMT reduced risk for PTSD relative to the no-training condition (odds ratio 3.13, 95% confidence interval 1.01–9.22, p < 0.05, number needed to treat = 19.2). No other between-group differences were found. The results were consistent across a variety of analytic techniques and data imputation approaches.ConclusionsFour sessions of ABMT, delivered prior to combat deployment, mitigated PTSD risk following combat exposure. Given its low cost and high scalability potential, and observed number needed to treat, research into larger-scale applications is warranted. The ClinicalTrials.gov identifier is NCT01723215.
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Tran, Alison H., and Garvin Lee. "Fondaparinux for Prevention of Venous Thromboembolism in Major Orthopedic Surgery." Annals of Pharmacotherapy 37, no. 11 (November 2003): 1632–43. http://dx.doi.org/10.1345/aph.1c104.
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OBJECTIVE: To review clinical information related to fondaparinux, a synthetic pentasaccharide recently approved for the prevention of deep-vein thrombosis (DVT) in patients undergoing major orthopedic surgeries and for extended DVT prophylaxis after hip fracture surgery. DATA SOURCES: Primary and review articles were identified by MEDLINE (1983–June 2003) using the key words pentasaccharide, Org31540, SR90107A, DVT prophylaxis, and fondaparinux. Additional sources were found listed in articles, abstracts, and unpublished data on file from the manufacturer. Articles selected were based on their coverage of the pharmacology, pharmacokinetics, safety, and efficacy of fondaparinux. STUDY SELECTION AND DATA EXTRACTION: All of the articles identified were evaluated and all information deemed relevant was included. DATA SYNTHESIS: Fondaparinux is a selective antithrombin-dependent, indirect inhibitor of activated factor Xa. It has a favorable and predictable pharmacokinetic profile when administered subcutaneously, and has a long half-life, allowing once-daily dosing. Fondaparinux lacks in vitro cross-reactivity with heparin-induced antibodies. Major Phase III studies have demonstrated that subcutaneous fondaparinux sodium 2.5 mg given at least 6 hours postoperatively resulted in a 55% reduction in the risk of venous thromboembolism (VTE) in patients undergoing hip fracture surgery, total hip replacement surgery, or knee replacement surgery compared with standard enoxaparin therapy. It has a safety profile similar to that of enoxaparin with respect to clinically relevant major bleeding, including fatal bleeding, nonfatal bleeding, and bleeding requiring repeat surgery. The use of fondaparinux for prolonged prophylaxis after hip fracture has demonstrated further reduction in VTE events without increasing the risk of bleeding. CONCLUSIONS: Fondaparinux is the first of a new class of synthetic factor Xa inhibitors that demonstrated greater efficacy compared with enoxaparin for the prevention of VTE in major orthopedic surgery without an increase in clinically relevant bleeding. Given the favorable cost-effectiveness analysis and improved efficacy profile, fondaparinux should be considered for formulary addition for DVT prophylaxis in patients undergoing hip and knee replacement surgery. In patients undergoing hip fracture surgery, fondaparinux should be considered the DVT prophylaxis of choice. Extended thromboprophylaxis up to 28 days resulted in additional reduction in VTE (both symptomatic and venography-proven DVT) in patients with hip fracture surgery.
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Avivi, Irit, Dina Stroopinsky, Jacob Rowe, David Avigan, and Tami Katz. "Induced CD4+CD25+ FOXP-3+ and CD8+CD25+ FOXP-3+t Cells Exhibit a Concurrent Expression of Effector and Selective Suppressive Capacities." Blood 112, no. 11 (November 16, 2008): 3501. http://dx.doi.org/10.1182/blood.v112.11.3501.3501.
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Abstract Naturally occurring regulatory T cells (Tregs), identified as CD4+CD25+FoxP-3+ cells, are known to modulate immunologic tolerance and inhibit primary T cell activation, and therefore, may protect against graft-versus-host disease (GvHD) following allograft. However, having a non-selective suppressive effect, Tregs administration following transplantation may also result in delayed immunological reconstitution and diminished graft-versus-tumor effect, leading to an increased risk of infections and disease relapse. The generation of suppressive T cells that could selectively inhibit GvHD whilst preserving immunity against malignant cells and infection would promote significant contribution to GvHD prevention and therapy. The aim of this study was to investigate the characteristics of T cells undergoing allogeneic stimulation, looking for a subpopulation with a more specific inhibition of host immunity. A negative selection of PBMCs with anti-CD25 magnetic beads resulted in the production of CD25+ cells (-Naturally occurring) and CD25−PBMCs. CD25− PBMCs were than stimulated with allogeneic DC for 5–6. The resultant CD4+CD25+ or CD8+CD25+ populations were isolated with magnetic beads and investigated for immunophenotypical markers, cytokine expression profile (FACS), cell proliferation, inhibitory capacity and anti-viral response (INF-gamma). The current study has shown that stimulation of CD25− T cells with allogeneic peripheral blood mononuclear or dendritic cells (DCs) induces generation of a large fraction of CD4+CD25+ and CD8+CD25+ T-cells. This process was found to be more rapid and prominent following DCs stimulation. The resultant cells exhibit a mixed phenotype, demonstrating expression of the regulatory marker, FoxP3, as well as the inflammatory cytokines, IL-2 and IFNγ. Similar to naturally occurring Tregs, the induced CD4+CD25+ and CD8+CD25+ have markedly inhibited alloreactive T cell expansion. However, in contrast to naturally occurring Tregs, the induced populations, did not suppress proliferation against the cytomegalovirus (CMV) recombinant protein, suggesting their potential for more selective inhibition of host immunity. Expanded naturally occurring CD4+CD25+T Induced CD4+CD25+T cells Induced CD8+CD25+T cells GITR + ++ ++ Immunophenotype CTLA-4 + ++ ++ FoxP-3 + ++ ++ Self-proliferation − − − Suppression rate Primary allogeneic stimuli + ++ ++ CMV recall antigen stimuli + − − Cytokine expression IL-2 − + + IFN-γ − ++ ++ Cytotoxic capacity (granzyme B) − − + According to these data, CD25− derived CD4+CD25+FOXP-3+ and CD8+CD25+ FOXP-3, appear to have a dual expression of both effector and selective suppressive capacities, and therefore, might be potentially ideal for the use as post-transplant GvHD prophylaxis.
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Tous, Monica, Raquel Ferrer-Lorente, and Lina Badimon. "Selective inhibition of sphingosine kinase-1 protects adipose tissue against LPS-induced inflammatory response in Zucker diabetic fatty rats." American Journal of Physiology-Endocrinology and Metabolism 307, no. 5 (September 1, 2014): E437—E446. http://dx.doi.org/10.1152/ajpendo.00059.2014.
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Obesity is associated with a state of chronic inflammation. The chemokine (C-C motif) ligand 5 (CCL5) has been proposed to modulate the inflammatory response in adipose tissue (AT). However, the mechanisms underlying CCL5 upregulation in AT remain undefined. The objective of the present study was to evaluate whether the enzyme sphingosine kinase-1 (SK1) would modulate the expression of CCL5 and other inflammatory biomarkers in primary adipocytes and its potential role in lipopolysaccharide (LPS)-induced AT inflammation in a rat model of diabetes. To address this, LPS-stimulated primary adipocytes and 3T3-L1 cells were treated with a SK inhibitor, and the expression of Ccl5 and other CC chemokines were studied. Moreover, the effect of SK1 knockdown on cytokine production was analyzed in 3T3-L1 cells by transfection of SK1-specific small-interfering RNA (siRNA). The anti-inflammatory effects of SK inhibitor in AT were also investigated in vivo using the Zucker lean normoglycemic control (ZLC) rats. LPS treatment stimulated Ccl5, IL-6, pentraxin 3 ( Ptx3), and Tnfα mRNA expression in primary adipocytes and 3T3-L1 cells, whereas pharmacologically and siRNA-mediated SK1 inhibition strongly reduced mRNA levels of proinflammatory cytokines in these cells. Similarly, administration of SK inhibitor to ZLC rats prevented the LPS-induced inflammatory response in AT. Our data demonstrate a role for SK1 in endotoxin-induced cytokine expression in adipocytes and suggest that inhibition of SK1 may be a potential therapeutic tool in the prevention and treatment of chronic and common metabolic disorders, including obesity, insulin-resistance, and type 2 diabetes.
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Jeethy Ram, T., Asha Lekshmi, Thara Somanathan, and K. Sujathan. "Galectin-3: A factotum in carcinogenesis bestowing an archery for prevention." Tumor Biology 43, no. 1 (May 14, 2021): 77–96. http://dx.doi.org/10.3233/tub-200051.
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Cancer metastasis and therapy resistance are the foremost hurdles in oncology at the moment. This review aims to pinpoint the functional aspects of a unique multifaceted glycosylated molecule in both intracellular and extracellular compartments of a cell namely galectin-3 along with its metastatic potential in different types of cancer. All materials reviewed here were collected through the search engines PubMed, Scopus, and Google scholar. Among the 15 galectins identified, the chimeric gal-3 plays an indispensable role in the differentiation, transformation, and multi-step process of tumor metastasis. It has been implicated in the molecular mechanisms that allow the cancer cells to survive in the intravascular milieu and promote tumor cell extravasation, ultimately leading to metastasis. Gal-3 has also been found to have a pivotal role in immune surveillance and pro-angiogenesis and several studies have pointed out the importance of gal-3 in establishing a resistant phenotype, particularly through the epithelial-mesenchymal transition process. Additionally, some recent findings suggest the use of gal-3 inhibitors in overcoming therapeutic resistance. All these reports suggest that the deregulation of these specific lectins at the cellular level could inhibit cancer progression and metastasis. A more systematic study of glycosylation in clinical samples along with the development of selective gal-3 antagonists inhibiting the activity of these molecules at the cellular level offers an innovative strategy for primary cancer prevention.
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Boyle, P. J., S. D. Shah, and P. E. Cryer. "Insulin, glucagon, and catecholamines in prevention of hypoglycemia during fasting." American Journal of Physiology-Endocrinology and Metabolism 256, no. 5 (May 1, 1989): E651—E661. http://dx.doi.org/10.1152/ajpendo.1989.256.5.e651.
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To dissect the mechanisms of the prevention of hypoglycemia during fasting, eight normal humans were studied after overnight and 3-day fasts. Prolonged fasting resulted in the expected decrements in base-line glucose production and plasma glucose, insulin, and C-peptide and increments in plasma glucagon, epinephrine, norepinephrine, growth hormone, and cortisol. After the overnight and 3-day fasts, insulin restoration (0.2 mU.kg-1.min-1) alone resulted in transient decrements in glucose production and only 15 and 19% decrements in plasma glucose, respectively. Selective glucagon deficiency (somatostatin infusion with insulin and growth hormone replacement) resulted in transient decrements in glucose production and additional 24 and 29% decrements in plasma glucose, respectively. Notably, plasma glucose plateaued under both fasting conditions in both instances. Combined alpha- and beta-adrenergic blockade (phentolamine and propranolol infusions) alone had no effect on glycemia under either fasting condition. However, progressive hypoglycemia developed during adrenergic blockade coupled with glucagon deficiency after the overnight fast (85 +/- 2 to 48 +/- 4 mg/dl, P less than 0.001) and after the 3-day fast (65 +/- 2 to 33 +/- 1 mg/dl, P less than 0.001). These were the result of both decrements in glucose production and increments in glucose clearance. Thus we conclude that during fasting 1) the prevention of hypoglycemia is not due solely to decreased insulin secretion. 2) Glucagon plays a primary counterregulatory role. Sympathochromaffin catecholamines are not normally critical but compensate and become critical when glucagon is deficient. Adrenomedullary epinephrine is probably the relevant catecholamine. 3) Other hormones, neurotransmitters, or substrate effects may, or may not, be involved; if they are, they appear to stand low in the hierarchy of glucoregulatory factors.
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Fabian, C. J., B. F. Kimler, J. R. Anderson, C. Chamberlain, M. S. Mayo, C. M. Zalles, J. A. O’Shaughnessy, H. T. Lynch, K. A. Johnson, and D. Browne. "Phase II breast cancer chemoprevention trial of the third generation selective estrogen receptor modulator arzoxifene." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 1001. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.1001.
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1001 Background: Arzoxifene (ARZ) is a third generation SERM with efficacy in metastatic breast cancer but lacking uterine agonist activity. Methods: We conducted a randomized, double-blind, placebo-controlled Phase II prevention trial in 199 high risk women assessing the effects of ARZ 20 mg/day on several risk biomarkers. Biomarkers, including cytomorphology of breast epithelial cells obtained by random periareolar FNA (RPFNA) were assessed at baseline and following 6 months of placebo or ARZ. Subjects were stratified by presence or absence of atypia, ER expression, BRCA1/2 mutation, as well as menopause status. Results: At entry, mean age was 47, 52% were premenopausal and 47% of postmenopausal women were taking HRT. Mean 10 year Gail was 6.8% and mean Masood cytology index score was 14.3. The ARZ and placebo groups were well matched. The protocol defined primary endpoint was a decrease in RPFNA cytology Masood index score by ≥3 points at 6 months and required 160 evaluable subjects for 81% power to detect a change from 30% to 52% of subjects showing improvement. For the 181 evaluable subjects, there was no significant difference in the proportion of women achieving ≥3 point improvement (19% placebo vs. 24% ARZ, p=0.46); or in change in mean index score (0.6 placebo vs. 0.9 ARZ, p=0.53). There was also no difference in grade 3 or 4 side effects or dropout prior to 6 months. However, comparing ARZ to placebo, there was favorable modulation of the two risk biomarkers, mammographic breast density (p=0.001) and IGF-1:IGFBP-3 ratio (p=0.001), and reduction in bone turnover biomarker osteocalcin (p= 0.002), but without an increase in endometrial thickness. Conclusions: Although improvement in cytomorphology after 6 months of ARZ was not shown, the acceptable side effect profile and favorable modulation of other biomarkers (breast density, IGF-1:IGFBP-3, osteocalcin) provides support for continued evaluation of ARZ as a breast cancer prevention agent. No significant financial relationships to disclose.
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Jackson, A., C. Wilkinson, M. Ranger, R. Pill, and P. August. "Can primary prevention or selective screening for melanoma be more precisely targeted through general practice? A prospective study to validate a self administered risk score." BMJ 316, no. 7124 (January 3, 1998): 34–38. http://dx.doi.org/10.1136/bmj.316.7124.34.
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Moxham, Lorna, Trevor Arnold, Aaron Coutts, Alice Michaels, and Robin Ray. "Cardiovascular Disease in Regional Queensland: A Case Study Identifying the Implications for Changing the Primary Health Care Educational Paradigm." Australian Journal of Primary Health 6, no. 1 (2000): 37. http://dx.doi.org/10.1071/py00004.
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Australia is perceived by many as the 'lucky' country and the image that has been portrayed to the rest of the world is one that projects a nation of tanned, active, healthy, and sports-loving individuals. This image is outdated and instead Australia is a nation with a national health problem. The health problem is having an impact which is increasingly problematic for governments. It has long been recognised that primary prevention, can be developed in two ways: by using a whole of population approach or through selective targeting (Naidoo & Wills, 1998). Within this context, this paper has chosen to explore and discuss a selective targeting approach through a case analysis of cardiovascular disease in regional Australia. In Australia, cardiovascular disease continues to be one of the major causes of death. This fact is a matter of great concern to all Australians but is particularly significant for people living in the regional city of Rockhampton, Central Queensland, where the death rate from cardiovascular disease is significantly higher than it is for the rest of the state of Queensland (354.4 deaths per 100,000 people per year compared with 310.6, Harper & Taylor, 1997, p. 21). The high death rate from heart disease in Queensland is even higher than the Australian average (Harper & Taylor, 1997, p. 22). Research previously conducted has revealed certain trends regarding cardiovascular disease. This research extends the available knowledge by measuring the cost in economic terms to the community. The findings explain the implications for Rockhampton employers and places regional health professionals in a better position to develop further research as well as to implement and explain alternative health strategies.
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Maguire, Anne, Jan E. Clarkson, Gail VA Douglas, Vicky Ryan, Tara Homer, Zoe Marshman, Elaine McColl, et al. "Best-practice prevention alone or with conventional or biological caries management for 3- to 7-year-olds: the FiCTION three-arm RCT." Health Technology Assessment 24, no. 1 (January 2020): 1–174. http://dx.doi.org/10.3310/hta24010.
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Background Historically, lack of evidence for effective management of decay in primary teeth has caused uncertainty, but there is emerging evidence to support alternative strategies to conventional fillings, which are minimally invasive and prevention orientated. Objectives The objectives were (1) to assess the clinical effectiveness and cost-effectiveness of three strategies for managing caries in primary teeth and (2) to assess quality of life, dental anxiety, the acceptability and experiences of children, parents and dental professionals, and caries development and/or progression. Design This was a multicentre, three-arm parallel-group, participant-randomised controlled trial. Allocation concealment was achieved by use of a centralised web-based randomisation facility hosted by Newcastle Clinical Trials Unit. Setting This trial was set in primary dental care in Scotland, England and Wales. Participants Participants were NHS patients aged 3–7 years who were at a high risk of tooth decay and had at least one primary molar tooth with decay into dentine, but no pain/sepsis. Interventions Three interventions were employed: (1) conventional with best-practice prevention (local anaesthetic, carious tissue removal, filling placement), (2) biological with best-practice prevention (sealing-in decay, selective carious tissue removal and fissure sealants) and (3) best-practice prevention alone (dietary and toothbrushing advice, topical fluoride and fissure sealing of permanent teeth). Main outcome measures The clinical effectiveness outcomes were the proportion of children with at least one episode (incidence) and the number of episodes, for each child, of dental pain or dental sepsis or both over the follow-up period. The cost-effectiveness outcomes were the cost per incidence of, and cost per episode of, dental pain and/or dental sepsis avoided over the follow-up period. Results A total of 72 dental practices were recruited and 1144 participants were randomised (conventional arm, n = 386; biological arm, n = 381; prevention alone arm, n = 377). Of these, 1058 were included in an intention-to-treat analysis (conventional arm, n = 352; biological arm, n = 352; prevention alone arm, n = 354). The median follow-up time was 33.8 months (interquartile range 23.8–36.7 months). The proportion of children with at least one episode of pain or sepsis or both was 42% (conventional arm), 40% (biological arm) and 45% (prevention alone arm). There was no evidence of a difference in incidence or episodes of pain/sepsis between arms. When comparing the biological arm with the conventional arm, the risk difference was –0.02 (97.5% confidence interval –0.10 to 0.06), which indicates, on average, a 2% reduced risk of dental pain and/or dental sepsis in the biological arm compared with the conventional arm. Comparing the prevention alone arm with the conventional arm, the risk difference was 0.04 (97.5% confidence interval –0.04 to 0.12), which indicates, on average, a 4% increased risk of dental pain and/or dental sepsis in the prevention alone arm compared with the conventional arm. Compared with the conventional arm, there was no evidence of a difference in episodes of pain/sepsis among children in the biological arm (incident rate ratio 0.95, 97.5% confidence interval 0.75 to 1.21, which indicates that there were slightly fewer episodes, on average, in the biological arm than the conventional arm) or in the prevention alone arm (incident rate ratio 1.18, 97.5% confidence interval 0.94 to 1.48, which indicates that there were slightly more episodes in the prevention alone arm than the conventional arm). Over the willingness-to-pay values considered, the probability of the biological treatment approach being considered cost-effective was approximately no higher than 60% to avoid an incidence of dental pain and/or dental sepsis and no higher than 70% to avoid an episode of pain/sepsis. Conclusions There was no evidence of an overall difference between the three treatment approaches for experience of, or number of episodes of, dental pain or dental sepsis or both over the follow-up period. Future work Recommendations for future work include exploring barriers to the use of conventional techniques for carious lesion detection and diagnosis (e.g. radiographs) and developing and evaluating suitable techniques and strategies for use in young children in primary care. Trial registration Current Controlled Trials ISRCTN77044005. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 1. See the NIHR Journals Library website for further project information.
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Zhang, Li, Shun Lu, Ji Feng Feng, Arunee Dechaphunkul, Salvatore Chessari, Corinna Lanzarotti, Karin Jordan, and Matti S. Aapro. "Phase III study of NEPA, a fixed combination of netupitant and palonosetron, versus an aprepitant regimen for prevention of chemotherapy-induced nausea and vomiting (CINV)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 10090. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.10090.
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10090 Background: Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize CINV control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a novel fixed combination of a highly selective NK1 receptor antagonist (RA), netupitant (300 mg), and palonosetron (PALO 0.50 mg), a pharmacologically distinct 5-HT3RA, has shown superior CINV prevention compared to PALO in cisplatin and AC-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen, with the primary objective being to demonstrate non-inferiority in preventing CINV. Methods: This randomized, double-blind, parallel group Phase III study conducted in an Asian population was designed to compare efficacy and safety of a single oral dose of NEPA with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis, no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at -10%. Secondary efficacy endpoints included no emesis and no significant nausea (NSN: < 25mm on 100mm VAS). Results: Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR; no emesis and NSN rates favored NEPA. Most frequent study drug-related adverse events (AEs) for NEPA included constipation (8.0%) and hiccups (2.7%). The type/incidence/severity of AEs were similar for NEPA and APR/GRAN. Conclusions: In this first study comparing NK1RA regimens and 4 days of DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC. [Table: see text]
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Safri, Lenny Suryani, Henry Tan Chor Lip, M. Iqbal Saripan, Tan Jih Huei, K. Krishna, Mohamad Azim Md Idris, and Hanafiah Harunarashid. "Older age and duration of exposure to type 2 diabetes in selective screening of asymptomatic carotid artery stenosis for primary stroke prevention—A single institution experience." Primary Care Diabetes 14, no. 4 (August 2020): 364–69. http://dx.doi.org/10.1016/j.pcd.2019.10.001.
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Bejaoui, Mohamed, Mohamed Amine Zaouali, Rim Sakly, and Hassen Ben Abdennebi. "Olprinone protects the liver from ischemia–reperfusion injury through oxidative stress prevention and protein kinase Akt activation." Canadian Journal of Physiology and Pharmacology 96, no. 3 (March 2018): 227–31. http://dx.doi.org/10.1139/cjpp-2017-0153.
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Liver ischemia–reperfusion (IR) injury is inevitable in surgical procedures such as hepatic resection and liver transplantation. It represents a leading cause of liver graft dysfunction and primary nonfunction after transplantation. Phosphodiesterase (PDE) inhibitors are emerging as effective drugs able to reduce IR damage. The aim of this study was to investigate the effect of selective PDE-3 inhibitor olprinone (Olp) against liver IR injury. Male Wistar rats were subjected to 1 h of partial warm ischemia (70%) followed by 6 h of reperfusion. Before ischemia, rats were treated with saline (IR group), Olp (Olp group), or Olp with Akt inhibitor LY294002 (Olp plus LY group). After reperfusion, hepatic injury (transaminase activities), mitochondrial damage (glutamate dehydrogenase activity), oxidative stress (malondialdehyde and glutathione concentrations and catalase and superoxide dismutase activities), and protein kinase Akt activation were evaluated. Rat treatment with Olp reduced liver injury, prevented mitochondrial damage, decreased lipid peroxidation, and enhanced antioxidant enzymes. Also, Olp induced a significant activation in protein kinase Akt. Inhibition of Akt with LY294002 abolished all of the protective effects of Olp. In conclusion, Olp treatment may be an effective strategy in reducing liver IR injury through oxidative stress prevention and Akt activation.
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Viviani, Giorgio Luciano, Franco Dallegri, Alessandra Quercioli, Edvige Veneselli, François Mach, Marisol Mirabelli-Badenier, Vincent Braunersreuther, and Fabrizio Montecucco. "CC and CXC chemokines are pivotal mediators of cerebral injury in ischaemic stroke." Thrombosis and Haemostasis 105, no. 03 (2011): 409–20. http://dx.doi.org/10.1160/th10-10-0662.
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SummaryThe definition of ischaemic stroke has been recently updated as an acute episode of neurological dysfunction caused by focal brain, spinal cord, or retinal ischaemia in the presence of a cerebral infarction. This “tissular” definition has highlighted the importance of pathophysiological processes underlying cerebral damage. In particular, post-ischaemic inflammation in the brain and in the blood stream could influence crucial steps of the tissue injury/repair cascade. CC and CXC chemokines orchestrate the inflammatory response in atherosclerotic plaque vulnerability and cerebral infarction. These molecules exert their activities through the binding to selective transmembrane receptors. CC and CXC chemokines modulate crucial processes (such as inflammatory cell recruitment and activation, neuronal survival, neoangio-genesis). On the other hand, CXC chemokines could also modulate stem cell homing, thus favouring tissue repair. Given this evidence, both CC and CXC chemokines could represent promising therapeutic targets in primary and secondary prevention of ischaemic stroke. Only preliminary studies have been performed investigating treatments with selective chemokine agonists/antagonists. In this review, we will update evidence on the role and the potential therapeutic strategies targeting CC and CXC chemokines in the pathophysiology of ischaemic stroke.
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Teesson, Maree, Katrina E. Champion, Nicola C. Newton, Frances Kay-Lambkin, Cath Chapman, Louise Thornton, Tim Slade, et al. "Study protocol of the Health4Life initiative: a cluster randomised controlled trial of an eHealth school-based program targeting multiple lifestyle risk behaviours among young Australians." BMJ Open 10, no. 7 (July 2020): e035662. http://dx.doi.org/10.1136/bmjopen-2019-035662.
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IntroductionLifestyle risk behaviours, including alcohol use, smoking, poor diet, physical inactivity, poor sleep (duration and/or quality) and sedentary recreational screen time (‘the Big 6’), are strong determinants of chronic disease. These behaviours often emerge during adolescence and co-occur. School-based interventions have the potential to address risk factors prior to the onset of disease, yet few eHealth school-based interventions target multiple behaviours concurrently. This paper describes the protocol of the Health4Life Initiative, an eHealth school-based intervention that concurrently addresses the Big 6 risk behaviours among secondary school students.Methods and analysisA multisite cluster randomised controlled trial will be conducted among year 7 students (11–13 years old) from 72 Australian schools. Stratified block randomisation will be used to assign schools to either the Health4Life intervention or an active control (health education as usual). Health4Life consists of (1) six web-based cartoon modules and accompanying activities delivered during health education (once per week for 6 weeks), and a smartphone application (universal prevention), and (2) additional app content, for students engaging in two or more risk behaviours when they are in years 8 and 9 (selective prevention). Students will complete online self-report questionnaires at baseline, post intervention, and 12, 24 and 36 months after baseline. Primary outcomes are consumption of sugar-sweetened beverages, moderate-to-vigorous physical activity, sleep duration, sedentary recreational screen time and uptake of alcohol and tobacco use.Ethics and disseminationThis study has been approved by the University of Sydney (2018/882), NSW Department of Education (SERAP no. 2019006), University of Queensland (2019000037), Curtin University (HRE2019-0083) and relevant Catholic school committees. Results will be presented to schools and findings disseminated via peer-reviewed journals and scientific conferences. This will be the first evaluation of an eHealth intervention, spanning both universal and selective prevention, to simultaneously target six key lifestyle risk factors among adolescents.Trial registration numberAustralian New Zealand Clinical Trials Registry (ACTRN12619000431123), 18 March 2019.
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Terre, Lisa, Gary Globe, and Mark T. Pfefer. "How Much Health Promotion and Disease Prevention Is Enough? Should Chiropractic Colleges Focus on Efficacy Training in Screening for Family Violence?" Journal of Chiropractic Education 20, no. 2 (October 1, 2006): 128–37. http://dx.doi.org/10.7899/1042-5055-20.2.128.
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Introduction: Although family violence has been identified as a major public health issue, it has received little attention in the chiropractic literature. Accordingly, this article provides a conceptual overview on family violence, discusses the role of chiropractors in its detection, and raises several issues germane to chiropractic education that deserve further attention in future chiropractic publications. Methods: A selective review of the empirical literature on family violence was conducted with a focus on issues relevant to chiropractic training and professional identity. Results: Extrapolating from the research, several models for medical training and continuing education have been proposed that emphasize a multidisciplinary, developmental approach to infusing knowledge, skill building, and mentored practice experiences into professional education experiences. Conclusion: As chiropractors become more mainstream portal-of-entry providers, there is a clear need to translate the didactics of family violence into the clinical setting. Clinical education may provide students the opportunity to master basic competencies for managing challenging family violence problems. The clinical environment may be appropriate for inculcating skills commensurate with those of other primary care providers. Yet, the extent to which training priorities and approaches extrapolated from other health care disciplines should be accepted wholesale by the chiropractic profession merits further discussion, including issues around the professional identity of chiropractic, the impact of accreditation standards and practice guidelines on actual professional practice behaviors, and the possible limits and unintended consequences associated with expanding the traditional chiropractic scope of practice from a specialty to a primary care profession.
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Chi, David, Hari Singhal, Lewyn Li, Tengfei Xiao, Weihan Liu, Matthew Pun, Rinath Jeselsohn, et al. "Estrogen receptor signaling is reprogrammed during breast tumorigenesis." Proceedings of the National Academy of Sciences 116, no. 23 (May 20, 2019): 11437–43. http://dx.doi.org/10.1073/pnas.1819155116.
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Limited knowledge of the changes in estrogen receptor (ER) signaling during the transformation of the normal mammary gland to breast cancer hinders the development of effective prevention and treatment strategies. Differences in estrogen signaling between normal human primary breast epithelial cells and primary breast tumors obtained immediately following surgical excision were explored. Transcriptional profiling of normal ER+ mature luminal mammary epithelial cells and ER+ breast tumors revealed significant difference in the response to estrogen stimulation. Consistent with these differences in gene expression, the normal and tumor ER cistromes were distinct and sufficient to segregate normal breast tissues from breast tumors. The selective enrichment of the DNA binding motif GRHL2 in the breast cancer-specific ER cistrome suggests that it may play a role in the differential function of ER in breast cancer. Depletion of GRHL2 resulted in altered ER binding and differential transcriptional responses to estrogen stimulation. Furthermore, GRHL2 was demonstrated to be essential for estrogen-stimulated proliferation of ER+ breast cancer cells. DLC1 was also identified as an estrogen-induced tumor suppressor in the normal mammary gland with decreased expression in breast cancer. In clinical cohorts, loss of DLC1 and gain of GRHL2 expression are associated with ER+ breast cancer and are independently predictive for worse survival. This study suggests that normal ER signaling is lost and tumor-specific ER signaling is gained during breast tumorigenesis. Unraveling these changes in ER signaling during breast cancer progression should aid the development of more effective prevention strategies and targeted therapeutics.