Science.gov

Sample records for intensive lipid-lowering therapy

  1. [An updated overview of the high intensity lipid lowering therapy in high cardiovascular risk patients].

    PubMed

    Pedro-Botet, Juan; Pintó, Xavier

    2016-01-01

    Statins are highly effective drugs to decrease the plasma concentrations of atherogenic lipoproteins and prevent cardiovascular disease. The clinical practice guidelines recommend the use of high-intensity statins to lower LDL-cholesterol by at least 50% in patients with CVD and those at high cardiovascular risk. The recommendations for the treatment of hypercholesterolaemia by the ACC/AHA have led to a paradigm shift in cardiovascular prevention. These recommendations have abandoned the therapeutic goals of LDL-cholesterol, and recommend the treatment with statins of high or moderate intensity in four high cardiovascular risk groups. These recommendations are different from the European guidelines on cardiovascular disease prevention, in which their objectives are still towards LDL-cholesterol. This paper reviews this controversy from different angles and from the perspective of the Spanish Interdisciplinary Committee for Cardiovascular Disease Prevention. Intervention studies with high intensity statins in primary prevention, in patients with acute coronary syndrome, and with stable ischaemic heart disease are also described. Likewise, treatment with statins of high intensity is addressed in terms of their effectiveness in cardiovascular prevention and in terms of their safety, with particular attention to muscle effects, as well as taking into account the pharmacological characteristics of the different statins and the increased safety of those with less potential for interactions. Finally, new agents are described for the treatment of hypercholesterolaemia, with special emphasis on anti-PCSK9 monoclonal antibodies, a new therapeutic group for the treatment of hypercholesterolaemia that will offer a huge progress in the prevention of cardiovascular diseases. Copyright © 2015 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  2. Lipid-lowering therapy in older persons

    PubMed Central

    2015-01-01

    Numerous randomized, double-blind, placebo-controlled studies and observational studies have shown that statins reduce mortality and major cardiovascular events in older high-risk persons with hypercholesterolemia. The Heart Protection Study showed that statins reduced mortality and major cardiovascular events in high-risk persons regardless of the initial level of serum lipids, age, or gender. The updated National Cholesterol Education Program III guidelines state that in very high-risk persons, a serum low-density lipoprotein (LDL) cholesterol level of < 70 mg/dl (1.8 mmol/l) is a reasonable clinical strategy for moderately high-risk persons (2 or more risk factors and a 10-year risk for coronary artery disease of 10% to 20%), and the serum LDL cholesterol should be reduced to < 100 mg/dl (2.6 mmol/l). When LDL cholesterol-lowering drug therapy is used to treat high-risk persons or moderately high-risk persons, the serum LDL cholesterol should be reduced by at least 30% to 40%. The serum LDL cholesterol should be decreased to less than 160 mg/dl in persons at low risk for cardiovascular disease. Addition of other lipid-lowering drugs to statin therapy has not been demonstrated to further reduce cardiovascular events and mortality. PMID:25861289

  3. Lipid-lowering therapy: who can benefit?

    PubMed

    Lewis, Sandra J

    2011-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the US. Despite the decline in CVD-associated mortality rates in recent years, coronary heart disease (CHD) still causes one in every six deaths in this country. Because most CHD risk factors are modifiable (eg, smoking, hypertension, obesity, onset of type 2 diabetes, and dyslipidemia), cardiovascular risk can be reduced by timely and appropriate interventions, such as smoking cessation, diet and lifestyle changes, and lipid-modifying therapy. Dyslipidemia, manifested by elevated low-density lipoprotein cholesterol (LDL-C), is central to the development and progression of atherosclerosis, which can be silent for decades before triggering a first major cardiovascular event. Consequently, dyslipidemia has become a primary target of intervention in strategies for the prevention of cardiovascular events. The guidelines of the Adult Treatment Panel (ATP) III, updated in 2004, recommend therapeutic lifestyle changes and the use of lipid-lowering medications, such as statins, to achieve specific LDL-C goals based on a person's global cardiovascular risk. For high-risk individuals, such as patients with CHD and diabetic patients without CHD, an LDL-C target of < 100 mg/dL is recommended, and statin therapy should be considered to help patients achieve this goal. If correctly dosed in appropriate patients, currently approved statins are generally safe and provide significant cardiovascular benefits in diverse populations, including women, the elderly, and patients with diabetes. A recent primary prevention trial also showed that statins benefit individuals traditionally not considered at high risk of CHD, such as those with no hyperlipidemia but elevated C-reactive protein. Additional evidence suggests that statins may halt or slow atherosclerotic disease progression. Recent evidence confirms the pivotal role of statins in primary and secondary prevention.

  4. Pharmacogenomics of lipid-lowering therapies.

    PubMed

    Hu, Miao; Tomlinson, Brian

    2013-06-01

    Statins are the most widely used group of lipid-lowering drugs and they have been shown to be effective in the prevention of cardiovascular disease, primarily by reducing plasma low-density lipoprotein cholesterol concentrations and possibly through other pleiotropic effects. However, there are large variations in lipid responses to statins and some patients have intolerable muscle adverse drug reactions, which may in part be related to genetic factors. In the last decade, pharmacogenetic studies on statins ranging from the candidate gene approach to the more recent genome-wide association studies have provided evidence that genetic variations play an important role in determining statin responses. This review summarizes the current understanding on the pharmacogenomics of statins and other lipid-lowering drugs in current use.

  5. Percent reduction in LDL cholesterol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents

    PubMed Central

    Ridker, Paul M; Mora, Samia; Rose, Lynda

    2016-01-01

    % reduction directly relates to efficacy. These data support guideline approaches that incorporate % reduction targets for statin therapy as well as absolute targets, and might provide a structure for the allocation of emerging adjunctive lipid-lowering therapies such as PCSK9 inhibitors should these agents prove broadly effective for cardiovascular event reduction. PMID:26916794

  6. Evaluation of the lipid lowering ability, anti-inflammatory effects and clinical safety of intensive therapy with Zhibitai, a Chinese traditional medicine.

    PubMed

    Xu, Dan-yan; Shu, Jun; Huang, Quan-yue; Wasti, Binaya; Chen, Chen; Liu, Ling; Zhao, Shui-ping

    2010-07-01

    To evaluate the lipid lowering ability, anti-inflammatory effects and clinical safety of intensive therapy of the Chinese traditional medicine Zhibitai in subjects with moderate to high cardiovascular risk. A total of 169 subjects (96 males and 73 females, aged 55-72) having moderate to high cardiovascular risk were recruited and randomly divided into Zhibitai group (n=85), which received 480 mg of Zhibitai orally twice daily, and atorvastatin group (n=84), which received 10 mg of atorvastatin orally once a day. Blood lipoproteins, myocardial enzymes, liver and renal functions were measured before treatment started, and after 4 and 8 weeks of the treatment. High sensitivity C-reactive protein (hs-CRP), P-selectin, matrix metalloproteinase-9 (MMP-9) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured before and after the treatment. Plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly decreased, and high-density lipoprotein cholesterol (HDL-C) was increased in both groups, after 4 and 8 weeks of treatment (p<0.05 for all pairs). Interestingly, plasma triglycerides (TG) decreased in the Zhibitai group after 4 weeks of treatment but only decreased in the atorvastatin group after 8 weeks. Inflammatory factors such as hs-CRP, P-selectin, MMP-9 and sICAM-1 were significantly decreased in both groups after 8 weeks (p<0.01 for all pairs). Furthermore, there was no difference in myocardial enzymes, hepatic and renal function test parameters, incidence of myopathy or gastrointestinal tract symptoms in either group. Zhibitai therapy is a good alternative to statin therapy to reduce plasma cholesterol levels in subjects with moderate to high cardiovascular risk. Most importantly, Zhibitai is safe to use. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

  7. Effectiveness of lipid-lowering therapy in HIV patients.

    PubMed

    Martínez, Esteban; Leyes, Pere; Ros, Emilio

    2008-05-01

    The aim of this article is to analyse the effectiveness of lipid-lowering therapy in HIV-infected patients. Although data on prevention of cardiovascular disease in HIV-infected patients are limited, available evidence suggests that intervention guidelines should be similar to those that are recommended for the general population. The main target of lipid-lowering therapy is LDL cholesterol; therefore statins are the drugs of choice. The efficacy of statins in HIV-infected persons appears to be lower than expected, although adherence to statin therapy has not been well assessed. Statins combining high potency and little clinically meaningful interactions with antiretroviral therapy (pravastatin, fluvastatin, atorvastatin and rosuvastatin) should be preferred as initial therapy, though comparative studies in HIV-infected persons are scarce. A combination of a statin at medium doses with either ezetimibe or a fibrate other than gemfibrozil may result in more satisfactory results than higher doses of statin monotherapy when LDL cholesterol goals are difficult to achieve or there persist elevated triglycerides and low HDL cholesterol, respectively. Adequate choice and dosing of lipid-lowering drugs, given as isolated agents or in combination therapy, and care for good drug compliance in HIV-infected patients at moderate or high cardiovascular risk should help maximize their long-term health.

  8. Cardiovascular pharmacogenetics of antihypertensive and lipid- lowering therapies.

    PubMed

    Vanichakarn, P; Hwa, J; Stitham, J

    2014-01-01

    Recent changes to the clinical management guidelines for hypertension and hyperlipidemia have placed emphasis on prevention through the pharmacological control and reduction of cardiovascular risk factors. In conjunction with proper diet and lifestyle changes, such risk factor control necessitates the use of safe and effective pharmacotherapy. However, many patients fail to reach or maintain therapeutic goals due to inadequacy and/or variability in response to antihypertensive and lipid-lowering medications. Thus, given the contribution of both hypertension and hyperlipidemia in the development and progression of cardiovascular disease, a personalized approach to pharmacotherapy, as well as disease prevention, seems particularly prudent. With the advancement of cardiovascular pharmacogenetics, the aim is to identify genetic biomarkers of drug-response and disease-susceptibility in order to make informed and individualized decisions, improving patient care through proper drug selection and dosing.

  9. Lipid-lowering drug therapy in elderly patients.

    PubMed

    Berthold, Heiner K; Gouni-Berthold, Ioanna

    2011-01-01

    Coronary heart disease (CHD) is the leading cause of death among elderly patients and >80% of all coronary deaths occur in patients >65 years. Cerebrovascular events are also associated with older age. Since elevated cholesterol concentrations are a risk factor for cardiovascular disease, lipid-lowering drugs, especially statins, are in widespread use for prevention. There is substantial underutilization of statins in the elderly population although meta-analyses of randomized trials have shown that in elderly secondary prevention patients they reduce all-cause mortality by approximately 22%, CHD mortality by 30%, non-fatal myocardial infarction (MI) by 26% and stroke by 25% over a treatment period of 5 years. Relative risk reduction is greater or at least equal to the one in younger patients, but absolute risk reduction is greater in the elderly because the event rate is higher. The benefit from statin treatment seems to start beyond 1 year of treatment. Data on primary prevention in the elderly are less clear. There is a significant reduction in CHD events, CHD deaths and all-cause mortality but numbers needed to treat (NNT) are higher than in secondary prevention. Treatment decisions have to consider the individual patient's situation regarding multimorbidity, polypharmacy and patient wishes. Economic considerations have to be made in some health systems. Statins have no role in the prevention or the treatment of dementia. Statins are generally safe and safety is equal in younger and older age groups. Their prescription should not be denied to patients for reasons of age alone. Other lipid-lowering drugs play only a minor role in cardiovascular disease (CVD) event prevention because convincing outcome studies are largely missing. A primary prevention statin trial in the very elderly is urgently needed.

  10. The use of lipid-lowering therapy for secondary prevention in patients undergoing percutaneous coronary intervention

    PubMed Central

    Ma, Jessica M; Jackevicius, Cynthia A; Genus, Uchenwa; Dzavik, Vladimir

    2006-01-01

    BACKGROUND Recent literature suggests that lipid-lowering therapy may have an early beneficial effect among patients undergoing percutaneous coronary intervention (PCI) because the therapy decreases cardiac mortality, morbidity and possibly restenosis. OBJECTIVE The primary objective of the present study was to determine the proportion of PCI patients receiving lipid-lowering therapy at a large, tertiary-care referral centre. METHODS Patients undergoing a first PCI between August 2000 and August 2002 with corresponding inpatient medication information were included in the study. Patient demographics, procedural variables, and lipid-lowering and other evidence-based cardiac medication data were collected. A multiple logistical regression model was constructed to evaluate the factors associated with the use of lipid-lowering therapy. RESULTS Of the 3254 cases included in the analyses, 52% were elective, 44% were urgent or salvage, and 4% were emergent. The mean patient age was 63 years, and 73% of patients were male. Over 76% of patients were receiving lipid-lowering therapy at the time of PCI. Patient use of other medications was as follows: acetylsalicylic acid in 96%, beta-blocker in 80% and angiotensin-converting enzyme inhibitor in 59%. In the multiple regression analysis, variables significantly associated with lipid-lowering therapy use included hypercholesterolemia, beta-blocker use, angiotensin-converting enzyme inhibitor use, case urgency, prior coronary artery bypass graft surgery, age and sex. CONCLUSION Lipid-lowering therapy use rates exceeded those previously reported in the literature. Women and patients undergoing elective procedures appear to be treated less often with lipid-lowering therapy. There remains an opportunity to further optimize use in this high-risk cohort at time of PCI. PMID:16639478

  11. PCSK9 inhibitors: A new era of lipid lowering therapy

    PubMed Central

    Chaudhary, Rahul; Garg, Jalaj; Shah, Neeraj; Sumner, Andrew

    2017-01-01

    Hyperlipidemia is a well-established risk factor for developing cardiovascular disease (CVD). The recent American College of Cardiology and American Heart Association guidelines on lipid management emphasize treatment of individuals at increased risk for developing CVD events with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) at doses proven to reduce CVD events. However, there are limited options for patients who are either intolerant to statin therapy, develop CVD despite being on maximally tolerated statin therapy, or have severe hypercholesterolemia. Recently the Food and Drug Administration approved two novel medications for low-density lipoprotein (LDL)-cholesterol reduction: Evolocumab and Alirocumab. These agents target and inactivate proprotein convertase subtilsin-kexin type 9 (PCSK9), a hepatic protease that attaches and internalizes LDL receptors into lysosomes hence promoting their destruction. By preventing LDL receptor destruction, LDL-C levels can be lowered 50%-60% above that achieved by statin therapy alone. This review explores PCSK-9 biology and the mechanisms available to alter it; clinical trials targeting PCSK9 activity, and the current state of clinically available inhibitors of PCSK9. PMID:28289523

  12. Differences in synthesis and absorption of cholesterol of two effective lipid-lowering therapies

    PubMed Central

    Kasmas, S.H.; Izar, M.C.; França, C.N.; Ramos, S.C.; Moreira, F.T.; Helfenstein, T.; Moreno, R.A.; Borges, N.C.; Figueiredo-Neto, A.M.; Fonseca, F.A.

    2012-01-01

    Effective statin therapy is associated with a marked reduction of cardiovascular events. However, the explanation for full benefits obtained for LDL cholesterol targets by combined lipid-lowering therapy is controversial. Our study compared the effects of two equally effective lipid-lowering strategies on markers of cholesterol synthesis and absorption. A prospective, open label, randomized, parallel design study, with blinded endpoints, included 116 subjects. We compared the effects of a 12-week treatment with 40 mg rosuvastatin or the combination of 40 mg simvastatin/10 mg ezetimibe on markers of cholesterol absorption (campesterol and β-sitosterol), synthesis (desmosterol), and their ratios to cholesterol. Both therapies similarly decreased total and LDL cholesterol, triglycerides and apolipoprotein B, and increased apolipoprotein A1 (P < 0.05 vs baseline for all). Simvastatin/ezetimibe increased plasma desmosterol (P = 0.012 vs baseline), and decreased campesterol and β-sitosterol (P < 0.0001 vs baseline for both), with higher desmosterol (P = 0.007) and lower campesterol and β-sitosterol compared to rosuvastatin, (P < 0.0001, for both). In addition, rosuvastatin increased the ratios of these markers to cholesterol (P < 0.002 vs baseline for all), whereas simvastatin/ezetimibe significantly decreased the campesterol/cholesterol ratio (P = 0.008 vs baseline) and tripled the desmosterol/cholesterol ratio (P < 0.0001 vs baseline). The campesterol/cholesterol and β-sitosterol/cholesterol ratios were lower, whereas the desmosterol/cholesterol ratio was higher in patients receiving simvastatin/ezetimibe (P < 0.0001 vs rosuvastatin, for all). Pronounced differences in markers of cholesterol absorption and synthesis were observed between two equally effective lipid-lowering strategies. PMID:22801416

  13. Overcoming toxicity and side-effects of lipid-lowering therapies.

    PubMed

    Wilkinson, Michael J; Laffin, Luke J; Davidson, Michael H

    2014-06-01

    Lowering serum lipid levels is part of the foundation of treating and preventing clinically significant cardiovascular disease. Recently, the American Heart Association/American College of Cardiology released cholesterol guidelines which advocate for high efficacy statins rather than LDL-c goals for five patient subgroups at high risk for cardiovascular disease. Therefore, it is critical that clinicians have an approach for managing side-effects of statin therapy. Statins are associated with myopathy, transaminase elevations, and an increased risk of incident diabetes mellitus among some patients; connections between statins and other processes, such as renal and neurologic function, have also been studied with mixed results. Statin-related adverse effects might be minimized by careful assessment of patient risk factors. Strategies to continue statin therapy despite adverse effects include switching to another statin at a lower dose and titrating up, giving intermittent doses of statins, and adding non-statin agents. Non-statin lipid-lowering drugs have their own unique limitations. Management strategies and algorithms for statin-associated toxicities are available to help guide clinicians. Clinical practice should emphasize tailoring therapy to address each individual's cholesterol goals and risk of developing adverse effects on lipid-lowering drugs.

  14. Adherence to Sleep Apnea Therapy and Use of Lipid-Lowering Drugs

    PubMed Central

    Kuna, Samuel T.; Field, Samuel H.; Chen, Zhen; Gupta, Rajesh; Roche, Dominic F.; Christie, Jason D.; Asch, David A.

    2010-01-01

    Background: Evidence that continuous positive airway pressure (CPAP) reduces cardiovascular morbidity comes largely from observational studies. This association may be confounded if CPAP adherents are healthier in ways not measured by investigators. We assessed whether patients adhering to lipid-lowering medications were more adherent to CPAP. Methods: This was a retrospective cohort study undertaken at the Philadelphia Veterans Affairs (VA) Medical Center (2005-2006) of consecutive patients on lipid-lowering therapy newly initiating CPAP for obstructive sleep apnea. Adherence to medications dispensed via the VA closed-pharmacy system was measured as the proportion of days covered (≥80% vs < 80%) in the year prior to CPAP initiation. CPAP adherence was defined as ≥ 4 h/d of “mask-on” time, measured electronically daily during the first week of CPAP. We examined the association between medication adherence and CPAP adherence using multivariable logistic regression. Results: Complete data were available for 117 of 142 (81.5%) subjects. After adjustment for age, race, medical comorbidity, and sleep apnea-related clinical factors, subjects with low medication adherence demonstrated a 40.1% (95% CI, 30.0-51.0) probability of using CPAP ≥ 4 h/d compared with 55.2% (95% CI, 46.9-63.1) for subjects with adequate (≥80%) medication adherence (adjusted for comparison, odds ratio (OR) = 1.8 [95% CI, 1.0-3.3], P = .04). Married patients were more adherent to medications and CPAP; inclusion of this factor reduced to nonsignificance the association of medication and CPAP adherence (OR = 1.6 [95% CI, 0.9-2.8], P = .12). Conclusion: Patients consistently refilling lipid-lowering medications were more adherent to CPAP, suggesting that differences in medication adherence or other health-promoting behaviors should be investigated in future nonrandomized, observational studies linking CPAP adherence and cardiovascular outcomes. PMID:19820075

  15. Early Effects of Intensive Lipid-Lowering Treatment on Plaque Characteristics Assessed by Virtual Histology Intravascular Ultrasound

    PubMed Central

    Lee, Jung-Hee; Shin, Dong-Ho; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo

    2016-01-01

    Purpose The effects of short-term intensive lipid-lowering treatment on coronary plaque composition have not yet been sufficiently evaluated. We investigated the influence of short-term intensive lipid-lowering treatment on quantitative and qualitative changes in plaque components of non-culprit lesions in patients with acute coronary syndrome. Materials and Methods This was a prospective, randomized, open-label, single-center trial. Seventy patients who underwent both baseline and three-month follow-up virtual histology intravascular ultrasound were randomly assigned to either an intensive lipid-lowering treatment group (ezetimibe/simvastatin 10/40 mg, n=34) or a control statin treatment group (pravastatin 20 mg, n=36). Using virtual histology intravascular ultrasound, plaque was characterized as fibrous, fibro-fatty, dense calcium, or necrotic core. Changes in plaque components during the three-month lipid-lowering treatment were compared between the two groups. Results Compared with the control statin treatment group, there was a significant reduction in low-density lipoprotein cholesterol in the intensive lipid-lowering treatment group (-20.4±17.1 mg/dL vs. -36.8±17.4 mg/dL, respectively; p<0.001). There were no statistically significant differences in baseline, three-month follow-up, or serial changes of gray-scale intravascular ultrasound parameters between the two groups. The absolute volume of fibro-fatty plaque was significantly reduced in the intensive lipid-lowering treatment group compared with the control group (-1.5±3.4 mm3 vs. 0.8±4.7 mm3, respectively; p=0.024). A linear correlation was found between changes in low-density lipoprotein cholesterol levels and changes in the absolute volumes of fibro-fatty plaque (p<0.001, R2=0.209). Conclusion Modification of coronary plaque may be attainable after only three months of intensive lipid-lowering treatment. PMID:27401638

  16. Effect of intensive versus moderate lipid lowering on endothelial function and vascular responsiveness to angiotensin II in stable coronary artery disease.

    PubMed

    van der Harst, Pim; Wagenaar, Lodewijk J; Buikema, Hendrik; Voors, Adriaan A; Plokker, H W Thijs; Morshuis, Wim J; Six, A Jacob; Boonstra, Piet W; Nickenig, Georg; Wassmann, Sven; van Veldhuisen, Dirk J; van Gilst, Wiek H

    2005-11-15

    Recent evidence has demonstrated that intensive lipid-lowering therapy with a high-dose statin provides significant clinical benefit beyond moderate lipid-lowering therapy. However, dose-dependent effects of short-term statin therapy on vascular function have not been demonstrated. We studied endothelial function and vascular responsiveness to angiotensin II in patients who had coronary artery diseased and were randomized to receive low- or high-dose atorvastatin (10 or 80 mg, respectively) or placebo. Internal thoracic artery segments were obtained during coronary bypass surgery and studied in vitro. Endothelium-dependent vasodilation was increased with atorvastatin therapy (p = 0.035) but was significantly increased further in patients who received 80 mg compared with those who received 10 mg of atorvastatin (p = 0.05). Endothelium improvement was accompanied by decreased vascular response to angiotensin II (p = 0.039). These findings suggest a mechanism for the clinical benefit of intensive lipid-lowering treatment in coronary heart disease.

  17. Challenges in Oral Lipid-lowering Therapy: Position Document of the Spanish Society of Cardiology.

    PubMed

    Anguita Sánchez, Manuel; Castro Conde, Almudena; Cordero Fort, Alberto; García-Moll Marimón, Xavier; Gómez Doblas, Juan José; González-Juanatey, José R; Lidón Corbi, Rosa María; López-Sendón, José Luis; Mostaza Prieto, José; Rodríguez Padial, Luis

    2016-11-01

    Lipid-lowering therapy is one of the cornerstones of cardiovascular prevention and is one of the most effective strategies in the secondary prevention of ischemic heart disease. Nevertheless, the current treatment of lipid disorders, together with lifestyle changes, fails to achieve the targets recommended in clinical guidelines in a substantial proportion of patients. PCSK9 inhibitors have demonstrated safety and efficacy in the treatment of dyslipidemia. Due to their ability to reduce low-density lipoprotein cholesterol levels, these drugs have recently been approved for clinical use by Spanish regulatory agencies, with the aim of reducing cardiovascular risk in selected patient groups. Copyright © 2016 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

  18. Comparative Effects of Diet-Induced Lipid Lowering Versus Lipid Lowering Along With Apo A-I Milano Gene Therapy on Regression of Atherosclerosis.

    PubMed

    Wang, Lai; Tian, Fang; Arias, Ana; Yang, Mingjie; Sharifi, Behrooz G; Shah, Prediman K

    2016-05-01

    Apolipoprotein A-1 (Apo A-I) Milano, a naturally occurring Arg173to Cys mutant of Apo A-1, has been shown to reduce atherosclerosis in animal models and in a small phase 2 human trial. We have shown the superior atheroprotective effects of Apo A-I Milano (Apo A-IM) gene compared to wild-type Apo A-I gene using transplantation of retrovirally transduced bone marrow in Apo A-I/Apo E null mice. In this study, we compared the effect of dietary lipid lowering versus lipid lowering plus Apo A-IM gene transfer using recombinant adeno-associated virus (rAAV) 8 as vectors on atherosclerosis regression in Apo A-I/Apo E null mice. All mice were fed a high-cholesterol diet from age of 6 weeks until week 20, and at 20 weeks, 10 mice were euthanized to determine the extent of atherosclerosis. After 20 weeks, an additional 20 mice were placed on either a low-cholesterol diet plus empty rAAV (n = 10) to serve as controls or low-cholesterol diet plus 1 single intravenous injection of 1.2 × 10(12)vector genomes of adeno-associated virus (AAV) 8 vectors expressing Apo A-IM (n = 10). At the 40 week time point, intravenous AAV8 Apo A-IM recipients showed a significant regression of atherosclerosis in the whole aorta (P< .01), aortic sinuses (P< .05), and brachiocephalic arteries (P< .05) compared to 20-week-old mice, whereas low-cholesterol diet plus empty vector control group showed no significant regression in lesion size. Immunostaining showed that compared to the 20-week-old mice, there was a significantly reduced macrophage content in the brachiocephalic (P< .05) and aortic sinus plaques (P< .05) of AAV8 Apo A-IM recipients. These data show that although dietary-mediated cholesterol lowering halts progression of atherosclerosis, it does not induce regression, whereas combination of low-cholesterol diet and AAV8 mediated Apo A-I Milano gene therapy induces rapid and significant regression of atherosclerosis in mice. These data provide support for the potential feasibility of this

  19. Absolute risk of cardiovascular disease events, and blood pressure- and lipid-lowering therapy in Australia.

    PubMed

    Banks, Emily; Crouch, Simon R; Korda, Rosemary J; Stavreski, Bill; Page, Karen; Thurber, Katherine A; Grenfell, Robert

    2016-05-02

    To quantify absolute cardiovascular disease (CVD) risk and treatment in Australian adults. Cross-sectional representative study of 9564 people aged 18 years or more who had participated in the 2011-12 Australian National Health Measures Survey (response rate for those aged 45-74 years: 46.5%). Prior CVD was ascertained and 5-year absolute risk of a primary CVD event calculated (using the Australian National Vascular Disease Prevention Alliance algorithm; categories: low [< 10%], moderate [10-15%], and high [> 15%] risk) on the basis of data on medical history, risk factors and medications, derived from interviews, physical measurements, and blood and urine samples. Absolute CVD risk increased with age and was higher among men than women. Overall, 19.9% (95% CI, 18.5-21.3%) of Australians aged 45-74 years had a high absolute risk of a future CVD event (an estimated 1 445 000 people): 8.7% (95% CI, 7.8-9.6%) had prior CVD (estimated 634 000 people) and 11.2% (95% CI, 10.2-12.2%) had high primary CVD risk (estimated 811 000 people). A further 8.6% (95% CI, 7.4-9.8%, estimated 625 000) were at moderate primary CVD risk. Among those with prior CVD, 44.2% (95% CI, 36.8-51.6%) were receiving blood pressure- and lipid-lowering medications, 35.4% (95% CI, 27.8-43.0%) were receiving only one of these, and 20.4% (95% CI, 13.9-26.9%) were receiving neither. Corresponding figures for high primary CVD risk were 24.3% (95% CI, 18.3-30.3%); 28.7% (95% CI, 22.7-34.7%); and 47.1% (95% CI, 39.9-54.3%). About one-fifth of the Australian population aged 45-74 years (about 1.4 million individuals) were estimated to have a high absolute risk of a future CVD event. Most (estimated 970 000) were not receiving currently recommended combination blood pressure- and lipid-lowering therapy, indicating substantial potential for health gains by increasing routine assessment and treatment according to absolute CVD risk.

  20. Myotoxic reactions to lipid-lowering therapy are associated with altered oxidation of fatty acids.

    PubMed

    Phillips, Paul S; Ciaraldi, Theodore P; Kim, Dong-Lim; Verity, M Anthony; Wolfson, Tanya; Henry, Robert R

    2009-02-01

    Despite exceptional efficacy and safety, fear of muscle toxicity remains a major reason statins are underutilized. Evidence suggests that statin muscle toxicity may be mediated by abnormalities in lipid metabolism. To test the hypothesis that myotubes from patients intolerant of lipid-lowering therapies have abnormal fatty acid oxidation (FAO) responses we compared muscle from 11 subjects with statin intolerance (Intolerant) with muscle from seven statin-naive volunteers undergoing knee arthroplasty (Comparator). Gross muscle pathology was graded and skeletal muscle cell cultures were produced from each subject. FAO was assessed following treatment with increasing statin concentrations. There was no difference in muscle biopsy myopathy scores between the groups. Basal octanoate oxidation was greater in Intolerant than in Comparator subjects (P = 0.03). Lovastatin-stimulated palmitate oxidation tended to be greater for Intolerant compared to Control subjects' myotubes (P = 0.07 for 5 microM and P = 0.06 for 20 microM lovastatin). In conclusion abnormalities in FAO of Intolerant subjects appear to be an intrinsic characteristic of these subjects that can be measured in their cultured myotubes.

  1. Intensive lipid lowering in patients with rheumatoid arthritis and previous myocardial infarction: an explorative analysis from the incremental decrease in endpoints through aggressive lipid lowering (IDEAL) trial.

    PubMed

    Semb, Anne G; Holme, Ingar; Kvien, Tore K; Pedersen, Terje R

    2011-02-01

    Documentation on secondary prevention with statins in RA patients with coronary heart disease (CHD) is limited, despite the increased risk of CHD in RA. Our objective was to describe the effect of statin treatment on lipid levels and cardiovascular disease (CVD) events in patients with RA who participated in the incremental decrease in endpoints through aggressive lipid lowering (IDEAL) study. Patients with previous myocardial infarction (MI) were randomly assigned to atorvastatin 80 mg daily or simvastatin 20-40 mg daily and followed for 4.8 years. We focused on changes in lipid levels in the current exploratory analyses and used the composite secondary endpoint in the IDEAL study: any CVD event. Out of the 8888 patients in the IDEAL study, 87 had RA. RA patients had significantly lower baseline levels of total- and low-density lipoprotein (LDL) cholesterol than patients without RA; 4.8 + 1.0 vs 5.1 + 1.0 (P = 0.023) and 2.9 + 0.9 vs 3.1 + 0.9 mmol/l (P = 0.034) for total cholesterol and LDL, respectively. The lipid reductions with either simvastatin or atorvastatin were comparable. Cardiovascular events occurred in 23/87 (26.4%) of the RA patients compared with 2523/8801 (28.7%; P = 0.70) in the general IDEAL population. The occurrence of these events was not related to the duration of RA, age, gender or treatment assignment. Patients with RA and previous MI had comparable lipid-lowering effect and similar rates of cardiovascular events as those without RA, although the RA patients had lower baseline cholesterol levels than patients without RA.

  2. Patterns and effectiveness of lipid-lowering therapies in a managed care environment.

    PubMed

    Meyer, Jay W; Schultz, Jennifer S; O'Donnell, John C; Patel, Pankaj A; Sasane, Rahul M

    2005-01-01

    To investigate the effectiveness of statin therapy and to compare the effectiveness results of this study with the reported efficacy of the corresponding data from randomized clinical trials in a moderate-to-high risk coronary heart disease (CHD) managed care population. Subjects, > or = 18 years old, with a new hyperlipidemia diagnosis or a new prescription claim for a lipid-lowering medication (LLM) between January 1, 1999 and March 31, 2001 were followed for 12 months. Subjects were classified into six medication categories of LLM use based partly on efficacy levels on package inserts. CHD risk factors were measured in the 24-month period prior, and subjects were required to have an established CHD or a CHD-related condition, or have two or more CHD risk factors. The study population consisted of 39,124 hyperlipidemic subjects with moderate-to-high CHD risk; 22,048 (56.4%) were untreated with LLMs. Absolute mean low-density lipoprotein cholesterol (LDL-C) reductions ranged from a 32 mg/dL decrease in the low-efficacy groups to a 57 mg/dL decrease in the high efficacy statin group; percent reductions ranged from a 19% reduction from baseline to a 32% reduction from baseline, respectively. Less than half of subjects (47%) reached LDL goals set forth by NCEP Adult Treatment Panel (ATP III) guidelines, however, the rate of reaching goal increased as statin efficacy increased. While a dose-response relationship was observed, the effectiveness of statin therapy was less than stated in package labeling and only 72% of the users of the highest efficacy statins reached their ATP III goal. LLM use was inconsistent with that recommended by the NCEP ATP III CHD risk assessment. Hyperlipidemia treatment in the managed care setting remains in need of improvement.

  3. Effectiveness of lipid-lowering therapy among a sample of patients in Colombia.

    PubMed

    Machado-Alba, Jorge Enrique; Murillo-Muñoz, Maria Monica; Machado-Duque, Manuel Enrique

    2013-06-01

    To determine the effectiveness of lipid-lowering therapy in a sample of patients affiliated with the Sistema General de Seguridad Social en Salud (the Colombian health system). A cross-sectional study was conducted from 1 January 2010-30 June 2011. From a total of 8 316 patients in 10 cities, a random sample of 600 was stratified according to dyslipidemia. Information on sociodemographic and anthropometric characteristics, risk factors, and pharmacological and laboratory variables were obtained from medical records. Subjects were predominantly female (56.2%), with a mean age of 65.1 ± 11.5 years; 93.2% had hypertension; 29.0%, diabetes mellitus; and 10.2%, a history of myocardial infarction. The patients were being treated with lovastatin (84.1%) or gemfibrozil (12.3%)-both at doses below what is recommended-or atorvastatin (1.8%). In patients with high cardiovascular risk, 38.6% achieved goals for low-density lipoprotein cholesterol (LDL-C) levels (<100 mg/dL). Among those at moderate risk, 49.4% reached the target level (< 130 mg/dL). On average, there was a 4.9% reduction in LDL-C. Sex, age, history of cardiovascular disease and/or diabetes mellitus, use of hydrochlorothiazide, and poor therapy adherence were statistically associated with a lack of dyslipidemia control. Because a lack LDL-C control occurred in patients with two or more of the following variables: male, more than 55 years of age, diabetes and/or a history of cardiovascular disease, received lower doses of lovastatin, or non-adherent to treatment, it is recommended that medication be increased based on clearly-defined therapeutic goals and that comorbidities be assessed and effectively treated.

  4. Meta-analysis of lipid-lowering therapy in maintenance dialysis patients.

    PubMed

    Green, Darren; Ritchie, James P; Kalra, Philip A

    2013-01-01

    The use of lipid-lowering therapy (LLT) in patients on chronic dialysis is contentious. Here we present an aggregate data meta-analysis of randomised controlled trials (RCTs) comparing long-term LLT versus placebo in dialysis patients. A search of Medline, Google Scholar, COCHRANE database, EMBASE, and cardiovascular and nephrology society proceedings was performed. Criteria for inclusion were RCTs of LLT versus placebo, in which LLT was demonstrated to significantly reduce low-density lipoprotein cholesterol, >12 months of follow-up, and at least one cardiovascular or mortality endpoint in an independently reported dialysis population. Meta-analysis was performed for atherosclerotic cardiovascular events, stroke and mortality using a random-effects method for odds ratio (OR) of risk. Three studies were included with 7,051 patients (3,541 treatment and 3,510 placebo). Twenty-five percent of the LLT patients suffered an atherosclerotic cardiovascular event versus 27% for placebo. The OR was 0.89 (95% CI: 0.80-0.99, p = 0.04). For stroke (haemorrhagic and non-haemorrhagic combined), the figures were 6.2% (LLT) versus 5.7% (placebo) [OR = 1.11 (95% CI: 0.85-1.46, p = 0.45)]. For all-cause mortality, the figures were 40 versus 42% [OR = 0.97 (95% CI: 0.88-1.06, p = 0.49)]. There was an overall significant reduction in risk for atherosclerotic cardiovascular events in dialysis patients treated with LLT compared to placebo. There was a numerical but not a statistical reduction in mortality. There was no statistically significant increase in risk of stroke as has been previously reported. © 2014 S. Karger AG, Basel.

  5. Lipid lowering and imaging protease activation in atherosclerosis Lipid therapy and MMP imaging in atherosclerosis

    PubMed Central

    Challa, Azariyas; Zhang, Jiasheng; Golestani, Reza; Jung, Jae-Joon; Robinson, Simon; Sadeghi, Mehran M.

    2014-01-01

    Background Lipid lowering is a mainstay of modern therapeutic approach to atherosclerosis. We sought to evaluate matrix metalloproteinase (MMP)-targeted microSPECT imaging for tracking of the effect of lipid-lowering interventions on plaque biology in atherosclerotic mice in vivo. Methods and Results ApoE−/− mice fed on a high fat diet (HFD) for 2 months were randomly assigned to continuation of HFD, HFD plus simvastatin, HFD plus fenofibrate and high fat withdrawal (HFW). The animals underwent serial microSPECT/CT imaging using RP805, a 99mTc-labeled MMP-targeted tracer at 1 and 4 weeks after randomization. All three interventions reduced total blood cholesterol by 4 weeks. In animals on HFD, aortic arch RP805 uptake significantly increased from 1 week to 4 weeks. Tracer uptake in fenofibrate and HFW groups was significantly lower than uptake in the HFD group at 4 weeks. Similarly, CD 68 gene expression, reflecting plaque inflammation, was significantly lower in fenofibrate and HFW groups compared to HFD group. MMP tracer uptake significantly correlated with aortic CD68, but not VE-cadherin or smooth muscle α-actin expression. Conclusions MMP tracer uptake paralleled the effect of lipid-lowering interventions on plaque inflammation in atherosclerotic mice. MMP-targeted imaging may be used to track the effect of therapeutic interventions in atherosclerosis. PMID:24368425

  6. Comparison of current guidelines for primary prevention of coronary heart disease: risk assessment and lipid-lowering therapy.

    PubMed

    Broedl, Uli C; Geiss, Hans-Christian; Parhofer, Klaus G

    2003-03-01

    In primary prevention of atherosclerotic disease, it is difficult to decide when medical treatment should be initiated. The main goal of the study was to compare different guidelines for coronary heart disease (CHD) risk assessment and initiation of lipid-lowering therapy. Cross-sectional evaluation. An outpatient lipid and diabetes clinic in a university hospital. Risk factor data obtained on 100 consecutive patients (58 men and 42 women) without clinical evidence of cardiovascular disease were used to compare the Framingham risk equation, the U.S. National Cholesterol Education Program (Adult Treatment Panel III) (NCEP ATP III) guidelines, the joint European Societies guidelines, the joint British guidelines, the revised Sheffield table, and the Munster Heart Study calculator (PROCAM) CHD risk assessment and lipid-lowering therapy. Guidelines could be applied to different subsets of the cohort, ranging from 22% (PROCAM) to 95% of the cohort (revised Sheffield table). All guidelines (except PROCAM) could be applied to a total of 62 patients. Guidelines predicted > or =20% risk for developing CHD over 10 years in 53% (NCEP ATP III), 26% (European) and 32% (British), while Framingham predicted this risk level in 34%. CHD risk was estimated to be > or =3%/year in 5% according to Sheffield, while Framingham predicted this risk in 13%. Lipid-lowering drug therapy is recommended in 52% by NCEP ATP III, while European, British, and Sheffield guidelines recommend this in 26%, 35%, and 5%, respectively. Guidelines for assessing CHD risk and lipid-lowering therapy differ greatly. Therefore, these algorithms must be used with caution.

  7. The determinants of cost-effectiveness potential: an historical perspective on lipid-lowering therapies.

    PubMed

    Refoios Camejo, Rodrigo; McGrath, Clare; Miraldo, Marisa; Rutten, Frans

    2013-05-01

    The concept of cost effectiveness emerged in an attempt to link the prices of new healthcare technologies to the immediate value they provide, with payers defining the acceptable cost per unit of incremental effect over the alternatives available. It has been suggested that such measures allow developers to assess potential market profitability in an early stage of development, but may result in discouraging investment in efficient research if not used appropriately. The objective of this study is to identify the pattern of the factors determining cost effectiveness and assess the evolution of cost-effectiveness potential for drugs in development using lipid-lowering therapy as a case study. The study is based on observational clinical and market data covering a 20-year period (from 1990 to 2010) in the UK. Real-life clinical data including total cholesterol laboratory test results were extracted from the Clinical Practice Research Datalink (CPRD) and are used to illustrate how the clinical effectiveness of existing standard care changed over time in patients managed in clinical practice. Prescription Cost Analysis (PCA) data were extracted and the average price of the drug mix used was computed throughout the study period. Using this information, the maximum clinical benefit and cost savings to be had were estimated for each year of the analysis using a cost-effectiveness model. Subsequently, the highest price a new technology providing the maximum clinical effectiveness possible (i.e. eliminating cardiovascular risk from high cholesterol levels) could achieve under current cost-effectiveness rules was calculated and used as a measure of the potential cost effectiveness of drugs in development. The results in this study show that the total cholesterol values of patients managed in clinical practice moved steadily towards recommended clinical targets. Overall, the absolute potential for incremental health-related quality of life decreased by approximately 78

  8. Lipid-Lowering Therapy in HIV-Infected Patients: Relationship with Antiretroviral Agents and Impact of Substance-Related Disorders.

    PubMed

    Bednasz, Cindy; Luque, Amneris E; Zingman, Barry S; Fischl, Margaret A; Gripshover, Barbara M; Venuto, Charles S; Gu, Jie; Feng, Zekun; DiFrancesco, Robin; Morse, Gene D; Ma, Qing

    2016-01-01

    The use of combination antiretroviral therapy (cART) has significantly decreased the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. Lipid disorders, including lipodystrophy, hypertriglyceridemia, and hypercholesterolemia, remain the most commonly reported metabolic disorders among those treated with long-term cART. Mounting evidence suggests an association between drug abuse and poor glycemic control and diabetes complications. Substance related disorders (SRD) may increase the risk of metabolic syndrome. The aim of this retrospective cohort study was to examine the relationship between SRD, cART, and lipid-lowering agent use in an HIV infected population. Patients received efavirenz or protease inhibitor-based cART for at least 6 months. Prescription information was retrieved from the medical records. The primary outcome was the use of lipid-lowering agents including statins, fibrates and fish oil. The impact of SRD and cART was assessed on the lipid-lowering agent use. A total of 276 subjects with HIV infection were included, 90 (33%) received lipid-lowering agents, and 31 (34%) had SRD. Smoking was prevalent among subjects with SRD (84 vs 15%, p<0.001). Statins were the mainstay for the management of dyslipidemia (66%), followed by the fibrates (24%), omega-3 fatty acids (5%), nicotinic acid (3%) and the cholesterol absorption inhibitors (3%). Use of statins or fibrates was significantly higher among subjects without SRD than those with (40 vs 23%, p=0.005). The type of cART, including efavirenz and protease inhibitors, appeared to have no significant impact on the use pattern of lipid-lowering agents. Lopinavir/ritonavir (lopinavir/r) was mostly prescribed for subjects with SRD (25 vs 8%, p=0.02). Among HIV-infected patients, statins remain the mainstay for the management of dyslipidemia in routine clinical care, followed by fibrates. A significant high risk of metabolic disorders among patients with SRD is implicated by

  9. Lipid-lowering therapy in HIV-infected patients: relationship with antiretroviral agents and impact of substance-related disorders

    PubMed Central

    Bednasz, Cindy; Zingman, Barry S.; Luque, Amneris E.; Fischl, Margaret A.; Gripshover, Barbara M.; Venuto, Charles S.; Gu, Jie; Feng, Zekun; DiFrancesco, Robin; Morse, Gene D.; Ma, Qing

    2016-01-01

    BACKGROUND The use of combination antiretroviral therapy (cART) has significantly decreased the morbidity and mortality associated with HIV infection. Lipid disorders, including lipodystrophy, hypertriglyceridemia, hypercholesterolemia, and dyslipidemia, remain the most commonly reported metabolic disorders among those treated with long-term cART. Mounting evidence suggests an association between drug abuse and poor glycemic control and diabetes complications. Substance related disorders (SRD) may increase the risk of metabolic syndrome. MATERIALS AND METHODS The aim of this retrospective cohort study was to examine the relationship between SRD, cART, and lipid-lowering agent use in an HIV infected population. A total of 276 subjects with HIV infection were included, 90 (33%) received lipid-lowering agents, and 31 (34%) had SRD. Patients received efavirenz or protease inhibitor-based cART for at least 6 months. Prescription information was retrieved from the medical records. The primary outcome was the use of lipid-lowering agents including statins, fibrates and fish oil. The impact of SRD and cART was assessed on the lipid-lowering agent use. RESULTS Smoking was prevalent among subjects with SRD (84% vs. 15%, p<0.001). Statins were the mainstay for the management of dyslipidemia (66%), followed by the fibrates (24%), omega-3 fatty acids (5%), nicotinic acid (3%) and the cholesterol absorption inhibitors (3%). Use of statins or fibrates was significantly higher among subjects without SRD than those with (40% vs. 23%, p=0.005). The type of cART, including efavirenz and protease inhibitors, appeared to have no significant impact on the use pattern of lipid-lowering agents. Lopinavir/r was mostly prescribed for subjects with SRD (25% vs. 8%, p=0.02). CONCLUSIONS Among HIV-infected patients, statins remain the mainstay for the management of dyslipidemia in routine clinical care, followed by fibrates. A significant high risk of metabolic disorders among patients with

  10. Factors explaining the gender disparity in lipid-lowering treatment goal attainment rate in Chinese patients with statin therapy.

    PubMed

    Zhang, Rui; Zhao, Liancheng; Liang, Lirong; Xie, Gaoqiang; Wu, Yangfeng

    2012-05-29

    The lipid-lowering treatment goal attainment rate is lower for women than for men among Chinese patients, but the reasons for this disparity have not been fully explored yet. To elucidate the potential factors and the significance of their contributions towards the observed discrepancy in lipid-lowering treatment goal attainment rates between Chinese women and men. We used data from 1808 patients from 21 tertiary and 6 secondary hospitals in China who received and maintained statin therapy treatment for at least 2 months. Lipid-lowering treatment goal attainment was defined as low-density lipoprotein cholesterol (LDL- C) reaching the treatment targets recommended by the Chinese Guidelines on Prevention and Control of Dyslipidemia in Adults. Logistic Regression was used to explore possible factors associated with gender disparity in goal attainment rates, and to what extent each factor contributes. A total of 674 women and 1134 men were enrolled in the study. Women had a significantly lower LDL-C goal attainment rate than that of men (46.0% vs 53.8%, P = 0.002), particularly in high and very high CVD risk groups. Among high and very high risk patients, approximately 35%, 7%, 5%, and 5% of gender disparity in LDL-C goal attainment rate was attributable to the gender difference in baseline LDL-C level, cardiovascular co-morbidities and associated risk factors, socioeconomic status, and the dosage of statin treatment, respectively. Approximately 50% of the gender disparity remained unexplained by these factors. Although nearly half of the gender disparity in lipid-lowering treatment goal attainment rate can be explained by the gender differences in baseline lipid level, socioeconomic status, cardiovascular co-morbidities and associated risk factors, and the dosage of statin in high and very high CVD risk patients, the other half of the gender disparity remains unexplained and requires further study to fully understand what other factors are at play.

  11. The economics of hypercholesterolemia and lipid-lowering therapy: a brief historical tour.

    PubMed

    Oster, G

    1998-09-01

    The first formal economic evaluation of a lipid-lowering intervention was conducted almost 20 years ago. The field exploded in the mid-1980s following the publication of findings from the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), in which the bile-acid sequestrant, cholestyramine, was reported to reduce the incidence of coronary artery disease in adults with significant elevations in cholesterol. Almost all of the early pharmacoeconomic studies that followed focused on this agent. Later in the decade, the introduction of lovastatin, the first 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (or "statin"), revolutionized the treatment of hypercholesterolemia, as it was significantly more effective than earlier agents (as were the other statins that followed it). Pharmacoeconomic studies of the statins generally have reported that, despite their higher cost, they are significantly more cost-effective than bile acid sequestrants. Recent long-term clinical trials, such as the West of Scotland Coronary Prevention Study (WOSCOPS) and the Scandinavian Simvastatin Survival Study (4S), have provided firm evidence of the benefits of the statins in both the primary and secondary prevention of coronary artery disease. Formal economic evaluations were incorporated into most of these end-point studies-in contrast to morbidity and mortality trials of earlier lipid-lowering agents-and results from these evaluations are just now becoming available. The availability of primary economic data derived directly from large-scale, long-term clinical trials raises important questions about the future role of modeling in this area.

  12. Mixed dyslipidemia among patients using lipid-lowering therapy in French general practice: an observational study.

    PubMed

    Van Ganse, Eric; Laforest, Laurent; Burke, Thomas; Phatak, Hemant; Souchet, Thierry

    2007-08-01

    Low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TGs) are associated with an increased incidence of coronary heart disease (CHD). However, limited data are available about the prevalence of dyslipidemias related to LDL-C, HDL-C, and TGs among French patients treated with lipid-lowering agents. This paper describes the prevalence of various types of dyslipidemias among patients treated with lipid-lowering agents in French general practice. This was a cross-sectional, observational study conducted using retrospective data collection at the time of enrollment. Eligible patients were those treated pharmacologically for dyslipidemia in the Cegedim Strategic Data general practice network. Fasting lipid values and cardiovascular (CV) risk factors were gathered by investigators using an ad hoc questionnaire. European guidelines were used to define various types of dyslipidemias. Polytomous logistic regression was used to assess the associations between different dyslipidemias and diabetes mellitus, a history of CHD, and the number of CV risk factors. A total of 946 patients had a complete lipid profile and valid data for determining CV risk status. The mean (SD) age of these patients was 64.0 (9.9) years, and 55.7% of the patients were men. At least 1 abnormality in LDL-C, HDL-C, or TGs was present in 791 (83.6 %) of the 946 patients. The rates of elevated LDL-C, low HDL-C, and elevated TGs were 73.2%, 16.9%, and 30.3%, respectively (these groups are not mutually exclusive). Among those who did not reach the LDL-C goal, 38.7% had dyslipidemias with low HDL-C, elevated TGs, or both. Compared with having a normal lipid profile, each additional CV risk factor increased the likelihood of the following types of dyslipidemias: low HDL-C and/or elevated TGs, but normal LDL-C (odds ratio [OR], 1.36; 95% CI, 1.03-1.79); elevated LDL-C and TGs, but normal HDL-C (OR, 1.58; 95% CI, 1.24-2.02); and all 3 lipid abnormalities

  13. Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot ‘Prevention of Decline in Cognition after Stroke Trial’ (PODCAST) Randomised Controlled Trial

    PubMed Central

    Scutt, Polly; Blackburn, Daniel J.; Ankolekar, Sandeep; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M.; Ford, Gary A.

    2017-01-01

    Background Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. Methods In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R). Results We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. Conclusion In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. Trial Registration

  14. Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot 'Prevention of Decline in Cognition after Stroke Trial' (PODCAST) Randomised Controlled Trial.

    PubMed

    Bath, Philip M; Scutt, Polly; Blackburn, Daniel J; Ankolekar, Sandeep; Krishnan, Kailash; Ballard, Clive; Burns, Alistair; Mant, Jonathan; Passmore, Peter; Pocock, Stuart; Reckless, John; Sprigg, Nikola; Stewart, Rob; Wardlaw, Joanna M; Ford, Gary A

    2017-01-01

    Stroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial. In a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125-170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0-8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke's Cognitive Examination-Revised (ACE-R). We enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1-48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference -10·6/-5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference -0·54/-0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison. In patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted. ISRCTN ISRCTN85562386.

  15. Effectiveness of lipid-lowering therapy with statins for secondary prevention of atherosclerosis--guidelines vs. reality.

    PubMed

    Bożentowicz-Wikarek, Maria; Kocełak, Piotr; Smertka, Mike; Olszanecka-Glinianowicz, Magdalena; Chudek, Jerzy

    2012-01-01

    The aim of the study was to analyze the effectiveness of lipid-lowering therapy and therapeutic decisions made by physicians for patients not achieving LDL targets. 11,768 patients undergoing therapy with statins for secondary prevention of atherosclerosis participated in a two-visit survey. In subjects not achieving the LDL-target (< 100 mg/dl), further therapeutic decisions made by physicians were recorded. Initially the LDL-target was achieved by 7.8% of patients on simvastatin and by 18.0% on atorvastatin, of which 20.8% were treated with at least a 40 mg dose. The most common changes in therapy to improve effectiveness was substituting simvastatin for another statin (75.2%, usually atorvastatin), or increasing atorvastatin dosage (59.8%). Intensification of a low fat diet and weight reduction were more frequently recommended in treatment with atorvastatin than with simvastatin (59.8% vs. 55.9%, p < 0.001). After enhanced therapy, the LDL-target was achieved by 27.8% on simvastatin and by 35.0% on atorvastatin (p < 0.001). In those with LDL levels remaining above the target, substitution of simvastatin with atorvastatin (49.9%), or the increase of atorvastatin dose (41.4%) was recommended. As previously, life-style counseling was more frequent in patients on atorvastatin (66.1% vs. 45.7% p < 0.001). 1. The use of low dose statins and noncompliance with behavioral modification guidelines are responsible for the low levels of effectiveness found with lipid-lowering therapies. 2. Physicians prefer substitution of less effective statins over the increase of dose in patients not achieving LDL targets. 3. Life-style changes are under-prescribed by physicians and under-implemented by their patients.

  16. Development and Validation of a Model to Predict Absolute Vascular Risk Reduction by Moderate-Intensity Statin Therapy in Individual Patients With Type 2 Diabetes Mellitus: The Anglo Scandinavian Cardiac Outcomes Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Collaborative Atorvastatin Diabetes Study.

    PubMed

    Kaasenbrood, Lotte; Poulter, Neil R; Sever, Peter S; Colhoun, Helen M; Livingstone, Shona J; Boekholdt, S Matthijs; Pressel, Sara L; Davis, Barry R; van der Graaf, Yolanda; Visseren, Frank L J

    2016-05-01

    In this study, we aimed to translate the average relative effect of statin therapy from trial data to the individual patient with type 2 diabetes mellitus by developing and validating a model to predict individualized absolute risk reductions (ARR) of cardiovascular events. Data of 2725 patients with type 2 diabetes mellitus from the Lipid Lowering Arm of the Anglo Scandinavian Cardiac Outcomes Trial (ASCOT-LLA) study (atorvastatin 10 mg versus placebo) were used for model derivation. The model was based on 8 clinical predictors including treatment allocation (statin/placebo). Ten-year individualized ARR on major cardiovascular events by statin therapy were calculated for each patient by subtracting the estimated on-treatment risk from the estimated off-treatment risk. Predicted 10-year ARR by statin therapy was <2% for 13% of the patients. About 30% had an ARR of >4% (median ARR, 3.2%; interquartile range, 2.5%-4.3%; 95% confidence interval for 3.2% ARR, -1.4% to 6.8%). Addition of treatment interactions did not improve model performance. Therefore, the wide distribution in ARR was a consequence of the underlying distribution in cardiovascular risk enrolled in these trials. External validation of the model was performed in data from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT; pravastatin 40 mg versus usual care) and Collaborative Atorvastatin Diabetes Study (CARDS; atorvastatin 10 mg versus placebo) of 3878 and 2838 patients with type 2 diabetes mellitus, respectively. Model calibration was adequate in both external data sets, discrimination was moderate (ALLHAT-LLT: c-statistics, 0.64 [95% confidence interval, 0.61-0.67] and CARDS: 0.68 [95% confidence interval, 0.64-0.72]). ARRs of major cardiovascular events by statin therapy can be accurately estimated for individual patients with type 2 diabetes mellitus using a model based on routinely available patient characteristics. There is a wide distribution in ARR that

  17. Randomized, Placebo-Controlled Trial of Mipomersen in Patients with Severe Hypercholesterolemia Receiving Maximally Tolerated Lipid-Lowering Therapy

    PubMed Central

    McGowan, Mary P.; Tardif, Jean-Claude; Ceska, Richard; Burgess, Lesley J.; Soran, Handrean; Gouni-Berthold, Ioanna; Wagener, Gilbert; Chasan-Taber, Scott

    2012-01-01

    Objectives Mipomersen, an antisense oligonucleotide targeting apolipoprotein B synthesis, significantly reduces LDL-C and other atherogenic lipoproteins in familial hypercholesterolemia when added to ongoing maximally tolerated lipid-lowering therapy. Safety and efficacy of mipomersen in patients with severe hypercholesterolemia was evaluated. Methods and Results Randomized, double-blind, placebo-controlled, multicenter trial. Patients (n  = 58) were ≥18 years with LDL-C ≥7.8 mmol/L or LDL-C ≥5.1 mmol/L plus CHD disease, on maximally tolerated lipid-lowering therapy that excluded apheresis. Weekly subcutaneous injections of mipomersen 200 mg (n  = 39) or placebo (n  = 19) were added to lipid-lowering therapy for 26 weeks. Main outcome: percent reduction in LDL-C from baseline to 2 weeks after the last dose of treatment. Mipomersen (n = 27) reduced LDL-C by 36%, from a baseline of 7.2 mmol/L, for a mean absolute reduction of 2.6 mmol/L. Conversely, mean LDL-C increased 13% in placebo (n = 18) from a baseline of 6.5 mmol/L (mipomersen vs placebo p<0.001). Mipomersen produced statistically significant (p<0.001) reductions in apolipoprotein B and lipoprotein(a), with no change in high-density lipoprotein cholesterol. Mild-to-moderate injection site reactions were the most frequently reported adverse events with mipomersen. Mild-to-moderate flu-like symptoms were reported more often with mipomersen. Alanine transaminase increase, aspartate transaminase increase, and hepatic steatosis occurred in 21%, 13% and 13% of mipomersen treated patients, respectively. Adverse events by category for the placebo and mipomersen groups respectively were: total adverse events, 16(84.2%), 39(100%); serious adverse events, 0(0%), 6(15.4%); discontinuations due to adverse events, 1(5.3%), 8(20.5%) and cardiac adverse events, 1(5.3%), 5(12.8%). Conclusion Mipomersen significantly reduced LDL-C, apolipoprotein B, total cholesterol and non-HDL-cholesterol, and

  18. The Effect of Aggressive Versus Conventional Lipid-lowering Therapy on Markers of Inflammatory and Oxidative Stress

    PubMed Central

    van Haelst, Paul L.; Wobbes, Martgriet H.; Gans, Rijk O.; Zijlstra, Felix; May, Johan F.; Smit, Andries J.; Tervaert, Jan Willem Cohen; van Doormaal, Jasper J.

    2007-01-01

    Purpose Recent trial results are in favor of aggressive lipid lowering using high dose statins in patients needing secondary prevention. It is unclear whether these effects are solely due to more extensive lipid lowering or the result of the potentially anti-inflammatory properties of statins. We aimed to determine whether aggressive compared with conventional statin therapy is more effective in reducing systemic markers of inflammation and oxidative stress. Materials and methods This was a multi-centre, double-blind, placebo-controlled trial. Patients with previous cardiovascular disease, who did not achieve low density lipoprotein (LDL) cholesterol levels <2.6 mmol/l on conventional statin therapy (simvastatin 40 mg) were randomized to continue with simvastatin 40 mg or to receive atorvastatin 40 mg for 8 weeks and thereafter atorvastatin 80 mg for the final 8 weeks (aggressive treatment). Lipids, C-reactive protein, soluble cellular adhesion molecules, neopterin, von Willebrand Factor, and antibodies against oxidized LDL were measured at baseline and after 16 weeks. Results Lipid levels decreased significantly in the aggressive treatment group (LDL-C reduction 20.8%; P < 0.001), whereas a slight increase was observed in the conventional group (LDL-C increase 3.7%; P = 0.037). A significant reduction in antibodies against oxidized LDL was seen in the aggressive (13.4%; P < 0.001) and the conventional (26.8%; P < 0.001) group, but there was no difference between groups (P = 0.25). Furthermore, no significant differences in change in other biomarkers was observed between both groups. Conclusions This study does not support the hypothesis that a more profound reduction in inflammatory and oxidative stress contributes to the benefits of aggressive statin therapy. PMID:17342417

  19. The decreased achievement of therapeutic goal in lipid lowering therapy in obese and diabetic patients in Poland.

    PubMed

    Holecki, Michał; Handzlik-Orlik, Gabriela; Almgren-Rachtan, Agnieszka; Duława, Jan; Chudek, Jerzy

    2017-02-01

    Statins are used to reduce a cardiovascular risk. However, the effectiveness of the therapy in many cases remains unsatisfactory. Therefore, the aim of this study was to evaluate the influence of obesity and diabetes on the achievement of therapeutic goal in lipid-lowering therapy in patients with a various cardiovascular risk in the daily clinical practice. This study was conducted on the basis of questionnaires obtained from 7018 patients (41.4% obese, 65.9% viscerally obese and 25.3% diabetics) treated with statins for at least three months. The effectiveness of the treatment was assessed in a subgroup of 3218 patients with a full lipid profile. The LDL-cholesterol target, adjusted for cardiovascular risk, was obtained by 8.1% of patients, less frequently by those with a very high risk of a cardiovascular disease (3.7%), obesity (5.5%), visceral obesity (5.5%) and the type 2 diabetes (5.3%). The obese patients with type 2 diabetes were the least likely to reach the target (3.0%). Male gender, age, the body mass index (BMI)≥28kg/m(2), visceral obesity, type 2 diabetes, and a low/moderate statin dose prescription were independent factors decreasing the chance of reaching the low-density lipoprotein (LDL) cholesterol target. 1. The prescribed statin doses do not fully explain the lower frequency of achieving the recommended target in a lipid-lowering therapy in the obese patients and the diabetics. 2. In the daily clinical practice the doses of statins are frequently insufficient and not adjusted for a cardiovascular risk. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  20. Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study.

    PubMed

    Shepherd, James; Kastelein, John J P; Bittner, Vera; Deedwania, Prakash; Breazna, Andrei; Dobson, Stephen; Wilson, Daniel J; Zuckerman, Andrea; Wenger, Nanette K

    2008-04-15

    This subanalysis of the TNT (Treating to New Targets) study investigates the effects of intensive lipid lowering with atorvastatin in patients with coronary heart disease (CHD) with and without pre-existing chronic kidney disease (CKD). Cardiovascular disease is a major cause of morbidity and mortality in patients with CKD. A total of 10,001 patients with CHD were randomized to double-blind therapy with atorvastatin 80 mg/day or 10 mg/day. Patients with CKD were identified at baseline on the basis of an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) using the Modification of Diet in Renal Disease equation. The primary efficacy outcome was time to first major cardiovascular event. Of 9,656 patients with complete renal data, 3,107 had CKD at baseline and demonstrated greater cardiovascular comorbidity than those with normal eGFR (n = 6,549). After a median follow-up of 5.0 years, 351 patients with CKD (11.3%) experienced a major cardiovascular event, compared with 561 patients with normal eGFR (8.6%) (hazard ratio [HR] = 1.35; 95% confidence interval [CI] 1.18 to 1.54; p < 0.0001). Compared with atorvastatin 10 mg, atorvastatin 80 mg reduced the relative risk of major cardiovascular events by 32% in patients with CKD (HR = 0.68; 95% CI 0.55 to 0.84; p = 0.0003) and 15% in patients with normal eGFR (HR = 0.85; 95% CI 0.72 to 1.00; p = 0.049). Both doses of atorvastatin were well tolerated in patients with CKD. Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD.

  1. Favorable effect of optimal lipid-lowering therapy on neointimal tissue characteristics after drug-eluting stent implantation: qualitative optical coherence tomographic analysis.

    PubMed

    Jang, Ji-Yong; Kim, Jung-Sun; Shin, Dong-Ho; Kim, Byeong-Keuk; Ko, Young-Guk; Choi, Donghoon; Jang, Yangsoo; Hong, Myeong-Ki

    2015-10-01

    Serial follow-up optical coherence tomography (OCT) was used to evaluate the effect of optimal lipid-lowering therapy on qualitative changes in neointimal tissue characteristics after drug-eluting stent (DES) implantation. DES-treated patients (n = 218) who received statin therapy were examined with serial follow-up OCT. First and second follow-up OCT evaluations were performed approximately 6 and 18 months after the index procedure, respectively. Patients were divided into two groups, based on the level of low-density lipoprotein-cholesterol (LDL-C), which was measured at the second follow-up. The optimal lipid-lowering group (n = 121) had an LDL-C reduction of ≥50% or an LDL-C level ≤70 mg/dL, and the conventional group (n = 97). Neointimal characteristics were qualitatively categorized as homogeneous or non-homogeneous patterns using OCT. The non-homogeneous group included heterogeneous, layered, or neoatherosclerosis patterns. Qualitative changes in neointimal tissue characteristics between the first and second follow-up OCT examinations were assessed. Between the first and second follow-up OCT procedures, the neointimal cross-sectional area increased more substantially in the conventional group (0.4 mm(2) vs. 0.2 mm(2) in the optimal lipid-lowering group, p = 0.01). The neointimal pattern changed from homogeneous to non-homogeneous less often in the optimal lipid-lowering group (1.3%, 1/77, p < 0.001) than in the conventional group (15.3%, 11/72, p = 0.44). Optimal LDL-C reduction was an independent predictor for the prevention of neointimal pattern change from homogeneous to non-homogeneous (odds ratio: 0.05, 95% confidence interval: 0.01∼0.46, p = 0.008). Our findings suggest that an intensive reduction in LDL-C levels can prevent non-homogeneous changes in the neointima and increases in neointimal cross-sectional area compared with conventional LDL-C controls. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  2. High dose simvastatin exhibits enhanced lipid lowering effects relative to simvastatin/ezetimibe combination therapy

    USDA-ARS?s Scientific Manuscript database

    Technical Abstract: Background: Statins are the frontline in cholesterol reduction therapies; however use in combination with agents that possess complimentary mechanisms of action may achieve further reduce in LDL-C. Methods and Results: Thirty-nine patients were treated with either 80mg simvasta...

  3. The effect of the intensity of lipid-lowering medications on the LDL cholesterol treatment goals of Asian patients with dyslipidaemia in primary care.

    PubMed

    Tan, N C; Goh, C C; Goh, S C P; Koh, Y L E; Koh, K H

    2016-12-01

    Dyslipidaemia is the key risk factor for arthrosclerosis, leading to myocardial infarctions and strokes. Achieving LDL cholesterol (LDL-C) treatment goals using lipid-lowering therapy (LLT) mitigates such cardiovascular risks. This study aimed to determine the proportions and factors influencing patients with dyslipidaemia on LLT who achieved their recommended LDL-C treatment goals. Adult Asian patients with dyslipidaemia, aged 31-80 years, were enrolled in a questionnaire survey. Using simplified Framingham risk scores, these patients were classified into low (LR), medium (MR) and high (HR) cardiovascular risk groups. Their lipid-lowering therapy was classified into low-intensity (LI), medium-intensity (MI) and high-intensity (HI) groups according to the 2013 American College of Cardiology and American Heart Association (ACC/AHA) Blood Cholesterol Guidelines. Data on their demographic, clinical, self-reported attitude and adherence to LLT were correlated with their latest lipid profiles from their electronic health records. These data were analysed using chi-square test, or independent t-test where appropriate for categorical variables and continuous data. Logistic regression was used to identify factors relating to LDL-C goal attainment. Amongst the 917 patients treated with LLT, 60·9% were females and 56·2% aged >60 years. The commonest statins prescribed were simvastatin (77·7%), atorvastatin (15·3%), rosuvastatin (4·3%) and lovastatin (3·4%). Those who attained LDL-C treatment goals included 89·4%, 77·4% and 70% of the LR, MR and HR groups. Overall, 72·4% of the patients achieved LDL-C treatment goals. Despite 98·4% of them self-reported LLT adherence, only 85·5%, 69·5% and 50% of the LI, MI and HI subgroups attained the desired outcomes, respectively. Overall, 27·6% of patients with dyslipidaemia, including 30% of the HR group, did not achieve LDL-C treatment goals, despite on LLT. Addressing their concerns and adjusting medication doses of their

  4. Lipid lowering drug therapy in patients with coronary heart disease from 24 European countries--Findings from the EUROASPIRE IV survey.

    PubMed

    Reiner, Ž; De Backer, G; Fras, Z; Kotseva, K; Tokgözoglu, L; Wood, D; De Bacquer, D

    2016-03-01

    Since dyslipidaemia is one of the most important risk factors for coronary heart disease (CHD), lowering of LDL-cholesterol (LDL-C) causes significant reduction in morbidity and mortality, particularly in patients with established CHD. The aim of this survey was to assess how statins were prescribed in CHD patients at discharge after a coronary event from hospitals throughout Europe and how the intake of these drugs was reported by the patients when they were seen more than one year later in relationship with their achieved LDL-C levels. 6648 CHD patients' data from centres in 24 European countries were gathered using standardized methods. Lipid measurements were performed in one central laboratory. Patients were divided in three groups: high-intensity statin therapy, moderate or low intensity statin therapy and no statin therapy at all. 90.4% CHD patients were on statin therapy at the time of discharge from the hospital which decreased to 86% one year later. Only 37.6% of these patients were prescribed a high-intensity statin at discharge which even decreased to 32.7% later. In only 6 countries (all of them high-income countries) the number of patients on a high-intensity statin therapy increased substantially after the hospital discharge. It is worrying that statin therapy was discontinued in 11.6% and that only 19.3% of all CHD patients achieved target values of LDL-C < 1.8 mmol/L at the time of interview. Too many CHD patients with dyslipidaemia are still inadequately treated and most of these patients on statin therapy are not achieving the treatment targets. Therapeutic control of LDL-C is clearly related to the intensity of lipid lowering drug regimen after the CHD event indicating that a considerable potential still exists throughout Europe to reduce CHD mortality and morbidity rates through more efficient LDL-C lowering. Copyright © 2016. Published by Elsevier Ireland Ltd.

  5. Intensive lipid lowering may reduce progression of carotid atherosclerosis within 12 months of treatment: the METEOR study.

    PubMed

    Bots, M L; Palmer, M K; Dogan, S; Plantinga, Y; Raichlen, J S; Evans, G W; O'Leary, D H; Grobbee, D E; Crouse, J R

    2009-06-01

    to exert its beneficial effect on atherosclerosis progression during the first 12 months of treatment. This parallels the timing of event reduction seen in clinical trials and suggests that the efficacy of lipid lowering treatment on CIMT progression can be evaluated in trials with a duration of 1 year, given sufficient sample size, high precision of measurements and a treatment effect comparable to that seen in METEOR.

  6. Identifying patients at risk for coronary heart disease: implications from trials of lipid-lowering drug therapy.

    PubMed

    Isles, C G; Paterson, J R

    2000-09-01

    Abnormal lipid levels contribute significantly to the risk of coronary heart disease (CHD), which is increased further in the presence of other risk factors. The association between elevated low-density lipoprotein (LDL) cholesterol and CHD risk is well established, and large primary and secondary prevention studies of HMG-CoA reductase inhibitors (statins) have shown conclusively that lowering LDL cholesterol levels reduces CHD events and total mortality. Regardless of the intervention used (diet, surgery, drugs), reduction of plasma cholesterol has consistently produced a reduction in cardiovascular risk. Absolute benefit is greatest in those who are at highest risk initially, and trial results suggest that the lower the LDL cholesterol level achieved, at least down to LDL of 3.0 mmol/l, then the lower is the CHD event risk. Epidemiological data also point to the negative impact of other lipids on CHD risk. Low levels of high-density lipoprotein (HDL) and high levels of triglycerides (particularly in conjunction with an LDL/HDL ratio >5) are particularly strong risk factors for CHD. Thus, although prevention trials to date have primarily assessed the impact of LDL lowering on CHD events, the initial assessment of CHD risk should consider a more detailed atherogenic profile including HDL and triglyceride levels. A general approach to preventing cardiovascular disease should include strategies to reduce the overall CHD risk by lifestyle modification and management of modifiable risk factors such as smoking, hypertension and diabetes. Based on data from recent prevention studies, and because they are the most potent lipid-lowering agents available for lowering LDL cholesterol, statins have appropriately become the drug of choice for most patients with hyperlipidaemia who require drug therapy.

  7. Is Lipid Lowering Therapy an Independent Risk Factor for Venous Thromboembolism? A Population-Based Case-Control Study

    PubMed Central

    Ashrani, Aneel A.; Barsoum, Michel K.; Crusan, Daniel J.; Petterson, Tanya M.; Bailey, Kent R.; Heit, John A.

    2015-01-01

    Introduction The independent effect of lipid lowering therapy (LLT) on venous thromboembolism (VTE) risk is uncertain. Objective To test statin and non-statin LLT as potential VTE risk factors. Methods Using Rochester Epidemiology Project resources, we identified all Olmsted County, MN residents with objectively diagnosed incident VTE (cases) over the 13-year period, 1988–2000 (n=1340), and one to two matched controls (n=1538). We reviewed their complete medical records for baseline characteristics previously identified as independent VTE risk factors, and for statin and non-statin LLT. Using conditional logistic regression, we tested the overall effect of LLT on VTE risk and also separately explored the role of statin versus that of non-statin LLT, adjusting for other baseline characteristics. Results Among cases and controls, 74 and 111 received statin LLT, and 32 and 50 received non-statin LLT, respectively. Univariately, and after individually controlling for other potential VTE risk factors (i.e., BMI, trauma/fracture, leg paresis, hospitalization for surgery or medical illness, nursing home residence, active cancer, central venous catheter, varicose veins, prior superficial vein thrombosis, diabetes, congestive heart failure, angina/myocardial infarction, stroke, peripheral vascular disease, smoking, anticoagulation), LLT was associated with decreased odds of VTE (unadjusted OR= 0.73; p= 0.03). When considered separately, statin and non-statin LLT were each associated with moderate, non-significant lower odds of VTE. After adjusting for angina/myocardial infarction, each was significantly associated with decreased odds of VTE (OR= 0.63, p< 0.01 and OR= 0.61, p=0.04, respectively). Conclusions LLT is associated with decreased VTE risk after adjusting for known risk factors. PMID:25891841

  8. Relation of fish oil supplementation to markers of atherothrombotic risk in patients with cardiovascular disease not receiving lipid-lowering therapy.

    PubMed

    Franzese, Christopher J; Bliden, Kevin P; Gesheff, Martin G; Pandya, Shachi; Guyer, Kirk E; Singla, Anand; Tantry, Udaya S; Toth, Peter P; Gurbel, Paul A

    2015-05-01

    Fish oil supplementation (FOS) is known to have cardiovascular benefits. However, the effects of FOS on thrombosis are incompletely understood. We sought to determine if the use of FOS is associated with lower indices of atherothrombotic risk in patients with suspected coronary artery disease (sCAD). This is a subgroup analysis of consecutive patients with sCAD (n=600) enrolled in the Multi-Analyte, Thrombogenic, and Genetic Markers of Atherosclerosis study. Patients on FOS were compared with patients not on FOS. Lipid profile was determined by vertical density gradient ultracentrifugation (n=520), eicosapentaenoic acid+docosahexaenoic acid was measured by gas chromatography (n=437), and AtherOx testing was performed by immunoassay (n=343). Thromboelastography (n=419), ADP- and collagen-induced platelet aggregation (n=137), and urinary 11-dehydrothromboxane B2 levels (n=259) were performed immediately before elective coronary angiography. In the total population, FOS was associated with higher eicosapentaenoic acid+docosahexaenoic acid content (p<0.001), lower triglycerides (p=0.04), total very low-density lipoprotein cholesterol (p=0.002), intermediate-density lipoprotein cholesterol (p=0.02), and AtherOx levels (p=0.02) but not in patients on lipid-lowering therapy. Patients not on lipid-lowering therapy taking FOS had lower very low-density lipoprotein cholesterol, intermediate-density lipoprotein cholesterol, remnant lipoproteins, triglycerides, low-density lipoprotein cholesterol, AtherOx levels, collagen-induced platelet aggregation, thrombin-induced platelet-fibrin clot strength, and shear elasticity (p<0.03 for all). In clopidogrel-treated patients, there was no difference in ADP-induced aggregation between FOS groups. Patients on FOS had lower urinary 11-dehydrothromboxane B2 levels regardless of lipid-lowering therapy (p<0.04). In conclusion, the findings of this study support the potential benefit of FOS for atherothrombotic risk reduction in sCAD with

  9. Reversible and non-reversible cardiovascular risk in patients treated with lipid-lowering therapy: analysis of SEAS and JUPITER trials.

    PubMed

    Poli, A; Corsini, A

    2010-10-01

    A number of clinical trials have confirmed that statin treatment and, more generally, LDL-lowering treatment, are able to reduce CHD and CVD events in a wide range of clinical conditions associated with increased cardiovascular risk. However, the most recent trials have also identified patient groups in which lipid-lowering treatment shows a more limited preventive potential due to the "non-reversibility" of part of the cardiovascular risk, which dilutes the observed treatment effect by events that are not directly a consequence of atherosclerosis. The use of lipid-lowering therapy in these patients should be driven not only by their absolute risk, as suggested by the most recent American and European guidelines, but also by their overall clinical setting and by the evidence of benefit obtained in controlled trials in comparable populations. Copyright (c) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  10. The MYLIP p.N342S polymorphism is associated with response to lipid-lowering therapy in Brazilian patients with familial hypercholesterolemia

    PubMed Central

    Santos, Paulo C.J.L.; Morgan, Aline C.; Jannes, Cinthia E.; Krieger, José E.; Santos, Raul D.

    2014-01-01

    Background A previous study reported that the myosin regulatory light chain interacting protein (MYLIP) might serve as a novel therapeutic class for treating dyslipidemia. It contributes to variations in the levels of circulating low-density lipoprotein cholesterol (LDL-C), promoting the degradation of LDL–LDLR, thus limiting absorption. The effect of genetic variation in the MYLIP gene in a disease scenario characterized by mutations in the LDLR gene has not been previously evaluated. Objective The aim of this study was to assess the effect of the p.N342S variant on the response to lipid-lowering therapy in Brazilian patients with heterozygous familial hypercholesterolemia (FH). Patients and methods A total of 156 patients with heterozygous FH were followed up for 12 months and received lipid-lowering therapy (different doses of atorvastatin with the addition of ezetimibe in over half the patients of each genotype group). Cholesterol data were assessed, and analysis of the MYLIP rs9370867 (p.N342S) genotypes was carried out by melting curve analysis. Results Baseline total cholesterol and baseline LDL-C levels were not different between genotypes. After 1 year of treatment, LDL-C responses (expressed as mg/dl and as %) were significantly different among genotypes (AA: −79±68 and −39±27, GA: −60±79 and −27±32, and GG: −30±83 and −15±38; P=0.02 and 0.005, respectively). In addition, FH patients carrying the AA genotype were more likely to achieve LDL-C levels of less than 130 mg/dl after 1 year of treatment (75.0%) compared with patients with the GG and GA genotypes (34.5 and 34.8%, respectively; P=0.001). Conclusion Our study indicates that MYLIP p.N342S might be a pharmacogenetic marker for lipid-lowering therapy in patients with FH. PMID:25171759

  11. Adherence to lipid-lowering therapy and the use of preventive health services: an investigation of the healthy user effect.

    PubMed

    Brookhart, M Alan; Patrick, Amanda R; Dormuth, Colin; Avorn, Jerry; Shrank, William; Cadarette, Suzanne M; Solomon, Daniel H

    2007-08-01

    Patients who adhere to preventive therapies may be more likely to engage in a broad spectrum of behaviors consistent with a healthy lifestyle. Because many of these behaviors cannot be measured easily, observational studies of outcomes associated with the long-term use of preventive therapies are subject to the so-called "healthy user bias." To better understand this effect, the authors examined the association between adherence to statin therapy and the use of preventive health services in a Pennsylvania cohort of 20,783 new users of statins between 1996 and 2004. After adjustment for age, gender, and various comorbid conditions, patients who filled two or more prescriptions for a statin during a 1-year ascertainment period were more likely than patients who filled only one prescription to receive prostate-specific antigen tests (hazard ratio (HR)=1.57, 95% confidence interval (CI): 1.17, 2.19), fecal occult blood tests (HR=1.31, 95% CI: 1.12, 1.53), screening mammograms (HR=1.22, 95% CI: 1.09, 1.38), influenza vaccinations (HR=1.21, 95% CI: 1.12, 1.31), and pneumococcal vaccinations (HR=1.46, 95% CI: 1.17, 1.83) during follow-up. These results suggest that patients who adhere to chronic therapies are more likely to seek out preventive health services, such as screening tests and vaccinations. Further work is needed to identify study design and analysis methods that can be used to minimize the healthy user bias in studies of preventive therapies.

  12. The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

    PubMed Central

    Stellaard, Frans

    2017-01-01

    The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath) as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1) The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2) The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3) The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded. PMID:28321334

  13. Lipid-lowering therapy and lipid goal attainment in patients with metabolic syndrome in China: subgroup analysis of the Dyslipidemia International Study-China (DYSIS-China).

    PubMed

    Wang, Fan; Ye, Ping; Hu, Dayi; Min, Ying; Zhao, Shuiping; Wang, Yongjun; Mu, Yiming; Yan, Xiaowei; Li, Zhanquan; Wei, Yidong; Li, Jihu

    2014-11-01

    To objectively evaluate lipid-lowering therapy and low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goal attainment in metabolic syndrome (MetS) patients in China. Data regarding patient demographics, lipid-lowering agents, lipid parameters, and cardiovascular risk profiles were analyzed for 25,317 patients of the Dyslipidemia International Study-China. MetS was defined according to criteria of the NCEP-ATP III and the 2007 Chinese Guidelines on Prevention and Treatment of Dyslipidemia in Adults. The prevalence of MetS was 39.9% and 37.4% according to the NCEP-ATP III and 2007 Chinese Guidelines, respectively. LDL-C goal attainment occurred less frequently among MetS patients than in those without MetS (NCEP-ATP III: 46.9% vs 68.6%; 2007 Chinese Guidelines: 52.2% vs 67.1%; p < 0.001). Similar results were obtained for non-HDL-C goal attainment (2007 Chinese Guidelines: 51.0% vs 72.0%; p < 0.001). As the risk class increased, LDL-C and non-HDL-C goal attainment decreased. In multivariate logistic regression analysis, DM, CHD, ischemic cerebrovascular disease, and higher SBP were independently associated with failure to achieve LDL-C and non-HDL-C goal attainment. The type of lipid-lowering agent was not significantly correlated with LDL-C not at goal attainment but was correlated with non-HDL-C not at goal attainment. Goal attainment for both LDL-C and non-HDL-C occurs less frequently in MetS patients than in those without MetS. The residual risk due to elevated non-HDL-C levels should be considered in MetS patients. Strategies for controlling multiple risk factors in order to decrease the residual risk related to dyslipidemia in MetS patients should be recommended in future guidelines. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  14. The use of plaque score measurements to assess changes in atherosclerotic plaque burden induced by lipid-lowering therapy over time: the METEOR study.

    PubMed

    Peters, Sanne A E; Dogan, Soner; Meijer, Rudy; Palmer, Mike K; Grobbee, Diederick E; Crouse, John R; O'Leary, Daniel H; Evans, Gregory W; Raichlen, Joel S; Bots, Michiel L

    2011-01-01

    To evaluate whether plaque scoring measurements are able to track changes in atherosclerotic plaque burden over time and to study whether this is affected by lipid-lowering therapy. Data used were from METEOR (Measuring Effects on Intima-Media Thickness: an Evaluation Of Rosuvastatin), a randomized controlled trial of rosuvastatin 40 mg among 984 low-risk patients with modest carotid intima-media thickening (CIMT). In this analysis, duplicate ultrasound images from 12 carotid sites were collected at the baseline and end of the study from 495 European patients and were evaluated for plaque presence and severity. Plaques were scored from near and far walls of the 12 sites (0= none; 1= minimal; 2= moderate; 3= severe) and plaque scores (PS) were combined into two summary measures for each examination. The MeanMaxPS is the mean over the 12 carotid sites of the maximum score at each site and the MaxMaxPS reflects the most severe lesion at any site. Baseline MeanMaxPS and MaxMaxPS were 0.31 (SD: 0.20) and 1.15 (SD: 0.51), respectively. Changes in MeanMaxPS and MaxMaxPS significantly differed between rosuvastatin and placebo (mean difference: -0.03 [SE: 0.01; p =0.016] and -0.09 [SE: 0.04; p =0.027], respectively). In contrast to rosuvastatin, which demonstrated no change from the baseline, placebo showed significant progression in MeanMaxPS and MaxMaxPS (p =0.002; both). The plaque-scoring method proved capable of assessing the change in atherosclerotic plaque burden over time and proved useful to evaluate lipid-lowering in asymptomatic individuals with a low risk of cardiovascular disease and subclinical atherosclerosis.

  15. Improved glucose tolerance after effective lipid-lowering therapy with bezafibrate in a patient with lipoatrophic diabetes mellitus: a putative role for Randle's cycle in its pathogenesis?

    PubMed

    Panz, V R; Wing, J R; Raal, F J; Kedda, M A; Joffe, B I

    1997-03-01

    This report describes a patient with lipoatrophic diabetes mellitus (LDM), which is a rare clinical syndrome characterized by lipoatrophy and severe insulin resistance. Although a genetic abnormality is suspected in the development of LDM, no functional mutations in key domains of the insulin receptor gene were detected. Therapy was directed primarily at decreasing the availability of non-esterified fatty acids (NEFA), and thereby improving glucose tolerance (Randle's cycle), by the administration of a lipid-lowering drug, bezafibrate. Serial changes in fasting levels of the hormones of glucose homeostasis and lipids were measured, as well as glucose and insulin responses to a 75-g oral glucose challenge at onset and following 3 and 6 months of fibrate therapy. Progressive reductions in the patient's levels of triglycerides and NEFA were paralleled by an improvement in beta-cell function, a decrease in insulin resistance, and the attainment of normal glucose homeostasis. We conclude that the pathogenesis of LDM may be related primarily to abnormal regulation of lipid, rather than glucose, metabolism.

  16. Major CHD risk factors predominate among African-American women who are eligible for lipid-lowering drug therapy under the new ATP III guidelines.

    PubMed

    Koro, Carol E; L'italien, Gilbert J; Fedder, Donald O

    2004-10-01

    Coronary heart disease remains the leading cause of morbidity and death among African-Americans. We studied the cardiovascular risk factor distributions among African-American men and women deemed eligible for lipid-lowering treatment under the new Adult Treatment Panel Guidelines (ATPIII). A sub-sample of African-American NHANES III subjects aged 20-79 years, with known cardiovascular risk factors and LDL-C levels was identified (n=4,213). We assessed their eligibility for drug therapy using the new ATP III criteria and compared CHD risk factor distributions across gender. Both conservative and drug-optional LDL-C target levels were applied. An estimated 5.7 million African-Americans aged 20-79 are eligible for drug therapy under ATP III, and the overall eligibility prevalence is 24.3%; 47.8% are males and 52.2% are females (P<0.001). Of these, 1.87 million are eligible based on drug-optional LDL-C targets and 54.5% of these are female. Of treatment-eligible individuals, 61% of males versus 72% of females exhibited LDL-C > or =160 mg/dl (P=0.0001). The prevalence and levels of important CHD risk factors such as diabetes, hypertension, mean total and LDL-C cholesterol levels, and body mass index were all greater for eligible females compared to males despite lower absolute Framingham risk estimates for females. Among African-Americans, more women than men are eligible for treatment under the new ATP III guidelines. Eligibility in women is based primarily on diabetes and lipid levels rather than absolute Framingham risk, which seems to be underestimated in African-American women. As compensation for this underestimate, drug-optional (lower) targets should be applied to this population.

  17. [Secondary prevention of ischemic heart disease in the Cuidad Real Province, Spain. Effectiveness of lipid-lowering therapy in primary health care].

    PubMed

    2000-09-23

    The efficacy of lipid-lowering therapy (LLT) in ischemic heart disease (IHD) is well established. But there are some doubts about its effectiveness on Primary Health Care (PHC) where we develop the long-term control of this sickness and it is difficult to reproduce the terms of the clinical trials. Multicenter cross-sectional study designed to evaluate the control of dyslipidemia achieved in patients with IHD diagnosed more than a year ago in our geographic primary health care system. The total cholesterol (tC), LDL, triglyceride, HDL levels and tC/HDL were determined to analyze the impact of LLT. 205 patients were collected by 14 general practitioners in several PHC centers. The average lipid profiles recorded (tC: 218 mg/dl; LDL: 151 mg/dl; triglyceride: 136 mg/dl; HDL: 49 mg/dl, and tC/HDL: 4,8) were far to the recommended by the international guidelines. The ideal (LDL < 100 mg/dl) and the acceptable targets (LDL < 130) were achieved by 9 and 30%. The HDL was not assess in 26.4% of the patients. It had had slight improvement of the women profile risk by more elevated values of HDLc than men (54.4 mg/dl vs. 46.9 mg/dl; p = 0.0002). Only 98 patients (45.85%) receive LLT, while 70% presented LDL > 130 mg/dl. The average dose of hypolipidemiants was small and the combination therapy had been scanty used (2.7%). The hypolipidemic secondary prevention was incorrect, with a big gap between the efficacy of the LLT and the actual effectiveness. In the majority of cases (75-80%) the values exceeded the secondary prevention targets. In a quarter of patients had never existed a clearly defined therapeutic target because the levels of HDL and LDL were not assessed. It was not prescribed neither fitting drug doses nor combinations to reach lipidemic preventive levels.

  18. Trends in the Use of Nonstatin Lipid-Lowering Therapy Among Patients With Coronary Heart Disease: A Retrospective Cohort Study in the Medicare Population 2007 to 2011.

    PubMed

    Bittner, Vera; Deng, Luqin; Rosenson, Robert S; Taylor, Ben; Glasser, Stephen P; Kent, Shia T; Farkouh, Michael E; Muntner, Paul

    2015-10-27

    Nonstatin lipid-lowering therapy is adjunctive therapy for high-risk individuals on statins or monotherapy among those who cannot tolerate statins. This study determined time trends between 2007 and 2011 for statin and nonstatin lipid-lowering therapy (niacin, fibrates, bile acid sequestrants, and ezetimibe) use among Medicare beneficiaries with coronary heart disease (CHD) in light of emerging clinical trial evidence. We conducted a retrospective cohort study using the national 5% random sample of Medicare beneficiaries (n = 310,091). We created 20 cohorts of individuals with CHD, representing calendar quarters from 2007 through 2011, to assess trends in use of statins and nonstatin lipid-lowering medications. Statin use increased from 53.1% to 58.8% between 2007 and 2011. Ezetimibe use peaked at 12.1% and declined to 4.6% by the end of 2011, declining among both patients on statins (18.4% to 6.2%) and not on statins (5.0% to 2.4%). Fibrate use increased from 4.2% to 5.0%, bile acid sequestrants did not change significantly, and niacin use increased from 1.5% to 2.4% and then declined in late 2011. Use of nonstatin lipid-lowering therapy was less common at older age, among African Americans, patients with heart failure, and patients with a higher Charlson comorbidity score. Nonstatin lipid-lowering therapy use was more common among men and patients with diabetes, those who had cardiologist visits, and among those taking statins. Declining ezetimibe and niacin use but not fibrate therapy among Medicare beneficiaries with CHD coincides with negative clinical trial results for these agents. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  19. APOA1 and APOB polymorphisms and apolipoprotein concentrations as biomarkers of risk in acute coronary syndrome: Relationship with lipid-lowering therapy effectiveness.

    PubMed

    Casillas-Muñoz, Fidel; Valle, Yeminia; Muñoz-Valle, José Francisco; Martínez-Fernández, Diana Emilia; Reynoso-Villalpando, Gabriela Lizet; Flores-Salinas, Héctor Enrique; Llamas-Covarrubias, Mara Anaís; Padilla-Gutiérrez, Jorge Ramón

    2017-10-06

    Lipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population. Three hundred patients with ACS and 300 control subjects (CS) were included. Neither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; P<.001) and ApoB (167 vs. 136.9mg/dL; P<.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL). The rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  20. Common variants of HMGCR, CETP, APOAI, ABCB1, CYP3A4, and CYP7A1 genes as predictors of lipid-lowering response to atorvastatin therapy.

    PubMed

    Poduri, Aruna; Khullar, Madhu; Bahl, Ajay; Sehrawat, B S; Sharma, Yashpaul; Talwar, Kewal K

    2010-10-01

    There is interindividual variation in lipid-lowering response to statins. The objective of this study was to investigate whether common variation in genes involved in lipid and statin metabolism modify the effect of statins on serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol concentration in coronary artery disease (CAD) patients. We studied the association between 18 single-nucleotide polymorphisms (SNPs) in six genes (HMGCR, CETP, APOAI, ABCB1, CYP3A4, CYP7A1) in response to atorvastatin therapy (20 mg/day) in 265 newly diagnosed CAD patients using multivariable adjusted general linear regression. Variant alleles of ABCB1 (-41A/G), HMGCR SNP29 G/T, rs5908A/G, rs12916C/T, and CYP7A1-204A/C polymorphisms were significantly associated with attenuated LDL-C reduction and variant alleles of CETP TaqI, -629C/A, and APOAI PstI polymorphisms were associated with higher increase in high-density lipoprotein-cholesterol. A three-loci interaction model consisting of CYP7A1rs892871AA/APOAIPstIP1P1/HMGCR rs12916CT was a better predictor for LDL-C lowering, when compared with single polymorphisms analysis on statin response. Variant genotypes of APOAI -2500C/T, CETP 405I/V, and ABCB1 3435C/T showed higher risk of myocardial infarction events (p < 0.05) in a 1-year follow-up of CAD patients. These results suggest that SNPs in lipid and statin pathway genes are associated with reduced LDL-C lowering by statins and identify individuals who may be resistant to maximal LDL-C lowering by statins.

  1. Electronic messaging support service programs improve adherence to lipid-lowering therapy among outpatients with coronary artery disease: an exploratory randomised control study.

    PubMed

    Fang, Ronghua; Li, Xia

    2016-03-01

    To compare drug adherence to lipid-lowering therapy among outpatients with coronary artery disease who received information via short message service, via short message service and Micro Letter, or via phone only. Messaging applications and short message service are commonly used internationally. However, little is known about how coronary artery disease outpatients in China may benefit from receiving health education through these technologies. Random sampling method. Data were collected from March-December 2013. Subjects from Chengdu City, China, were randomised to three groups: short message service, short message service + Micro Letter, and phone (control). Appointment reminders and health information were delivered to patients in accordance with designations. After six months, adherence to statin prescriptions was compared among the groups by using the Morisky Medication Adherence Scale. Logistic regression analysis was applied to determine those independent variables that were related to adherence. The short message service and short message service + Micro Letter groups had better cumulative adherence (lower Morisky Medication Adherence Scale scores) after six months than phone group, and the short message service + Micro Letter group had better cumulative adherence (lower Morisky Medication Adherence Scale scores) than the short message service group. Female sex, older age and marriage show positive associations with adherence. Short message service and messaging applications, such as Micro Letter, are effective means of providing discharged patients with reminders and coronary artery disease-related health information. Implementation of a short message service + Micro Letter program can improve outpatient adherence to medication. This research offers useful information to help medical staff design effective interventions to improve medication compliance among coronary artery disease patients. © 2015 John Wiley & Sons Ltd.

  2. Analysis of lipid-lowering therapy and factors affecting regularity of statin intake in patients with cardiovascular disease enrolled in the PROFILE registry.

    PubMed

    Gaisenok, Oleg; Martsevich, Sergey; Tripkosh, Svetlana; Lukina, Yulia

    2015-02-01

    The aim of this study was to analyze the quality of lipid-lowering therapy in a cohort of patients with cardiovascular disease enrolled in a Moscow-based registry, and to analyze the factors affecting the regularity of statin administration in this patient category. The present study included all patients who successively sought medical advice in the Preventive Pharmacotherapy Department of the Ministry of Healthcare of the Russian Federation between May 1 and December 31, 2011 (n=274). Each patient was given a specially designed questionnaire in order to assess compliance with the prescribed treatment that included the following questions: (1) if they knew, according to the results of previous exams, that they had elevated cholesterol levels (yes, no, don't know); (2) what method of hypercholesterolemia correction they used (diet, medication, physical exercise, or other); (3) if they were taking any statins (regularly, no, irregularly); and (4) if yes, what statin preparation and what dose they were taking. Patients' compliance with statin therapy was assessed on the basis of the responses received and the regularity of statin intake. The influence of various factors on regularity of statin intake in patients with cardiovascular disease was assessed by calculating odds ratios (OR) and 95% confidence intervals (CI) for advanced age (>70 years) (OR 0.49); higher statin dose than standard (OR 0.49); hypertension (OR 1.659); history of acute cerebrovascular event (OR 2.019); diabetes (OR 1.023); coronary heart disease (CHD) (OR 4.357); history of myocardial infarction (MI) (OR 4.838); history of coronary angiography/percutaneous coronary intervention (PCI) (OR 5.167). Analysis of factors with impact on regular compliance with statin therapy showed that the following were most significant: CHD, history of MI, and history of PCI. Previous cerebrovascular events and presence of diabetes did not motivate these patients to take statins on a regular basis. Copyright © 2014

  3. Impact of statin therapy on central aortic pressures and hemodynamics: principal results of the Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) Study.

    PubMed

    Williams, Bryan; Lacy, Peter S; Cruickshank, J Kennedy; Collier, David; Hughes, Alun D; Stanton, Alice; Thom, Simon; Thurston, Herbert

    2009-01-06

    Statins reduce the risk of cardiovascular events in people with hypertension. This benefit could arise from a beneficial effect of statins on central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation-Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy, investigated this hypothesis in a prospective placebo-controlled study of treated patients with hypertension. CAFE-LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5 centers in the United Kingdom and Ireland. Radial artery applanation tonometry and pulse-wave analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo (change in brachial systolic blood pressure, -0.1 mm Hg [95% CI, -1.8 to 1.6], P=0.9; change in brachial pulse pressure, -0.02 mm Hg [95% CI, -1.6 to 1.6], P=0.9). Atorvastatin did not influence central aortic pressures (change in aortic systolic blood pressure, -0.5 mm Hg [95% CI, -2.3 to 1.2], P=0.5; change in aortic pulse pressure, -0.4 mm Hg [95% CI, -1.9 to 1.0], P=0.6) and had no influence on augmentation index (change in augmentation index, -0.4%; 95% CI, -1.7 to 0.8; P=0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, -1.3 to 1.8; P=0.7) compared with placebo. The effect of statin or placebo therapy was not modified by the blood pressure-lowering treatment strategy in the factorial design. Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT

  4. Familial hypercholesterolemia and estimation of US patients eligible for low-density lipoprotein apheresis after maximally tolerated lipid-lowering therapy.

    PubMed

    Vishwanath, Raghu; Hemphill, Linda C

    2014-01-01

    Familial hypercholesterolemia (FH), an autosomal-dominant inherited disorder, can occur in either the heterozygous (HeFH) or homozygous (HoFH) state, and is characterized by high levels of serum low-density lipoprotein cholesterol (LDL-C). Although potent statins and maximally tolerated lipid-lowering therapy (LLT) have greatly reduced the risk of premature coronary heart disease (CHD) and death, all patients with HoFH and many with severe HeFH remain far from treatment goals and are thus at risk of cardiovascular disease. LDL apheresis is the treatment of choice for these patients but remains underutilized. No formal studies or epidemiologic data have estimated the prevalence of HoFH. An HeFH prevalence of 1:500 and a simplified Hardy-Weinberg equilibrium model was used to determine the probability of finding HoFH as 1:1 million in the general population. A US population of approximately 314.8 million was used to determine the number of cases of HoFH and HeFH. The following key parameters were used to estimate the prevalence of severe HeFH: baseline pretreatment LDL-C level and distribution of patients with FH, posttreatment LDL-C level and distribution after maximally tolerated LLT, and baseline percentage of patients with HeFH who have CHD. We assumed an HeFH prevalence of 1:500 and used statistics for a Gaussian distribution after the posttreatment means and standard deviations of LDL-C levels in patients with HeFH receiving maximally tolerated LLT, as has been documented by data from clinical trials and cross-sectional studies. These estimates do not include the statin-intolerant population. The objective of this analysis was to determine the prevalence of the US population with severe HeFH with or without CHD who still will be eligible for LDL apheresis despite maximally tolerated LLT. We estimated that there are 315 US patients with HoFH and 650,000 with HeFH. The estimated prevalence of the severe HeFH population eligible for apheresis is approximately 1

  5. Lipid Lowering Agents Aeromedical Concerns

    DTIC Science & Technology

    2001-06-01

    for those military concomitant measurement of triglyceride levels, aviators at high risk for CHD , in the second and Provided triglyceride levels are...The major classes of lipid lowering drugs are: protein levels are listed in Table 1. a. Bile acid sequestrants (cholestyramine, Risk Factors for...Level Level First CHD >200  >100  Second Without CHD , and with 2 or more risk >250  >130  factors, or genetically determined

  6. Lipid-lowering therapy and the patient with multiple risk factors: what have we learned from the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)?

    PubMed

    Sever, Peter S

    2005-12-01

    The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was the first trial of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) to assess the benefits of lipid lowering in the primary prevention of coronary heart disease (CHD) in patients with hypertension who were not deemed to have dyslipidemia by conventional measures. A total of 19,342 patients with hypertension and > or =3 cardiovascular risk factors, but without CHD, were enrolled in ASCOT. Of these, 10,305 patients with a serum cholesterol level of < or =250 mg/dL (< or =6.5 mmol/L) were randomized to either atorvastatin (10 mg/day) or placebo in the ASCOT lipid-lowering arm (ASCOT-LLA). Follow-up was planned for an average of 5 years. The ASCOT-LLA was stopped after 3.3 years owing to the superiority of atorvastatin 10 mg over placebo in reducing the primary end point of nonfatal myocardial infarction (MI) and fatal CHD. Patients receiving atorvastatin experienced a significant reduction in total cholesterol (50 mg/dL [1.3 mmol/L]) and low-density lipoprotein cholesterol (46 mg/dL [1.2 mmol/L]) levels after 1 year compared with those who received placebo. Cholesterol lowering with atorvastatin was associated with a highly significant reduction in the primary end point of nonfatal MI and fatal CHD (36%, P = 0.0005). The observed benefit was consistent across the secondary end points and the 18 prespecified subgroups. The ASCOT-LLA findings have influenced lipid-lowering guidelines and support the concept that treatment strategies to reduce cardiovascular disease should be based on the assessment of all cardiovascular risk factors, rather than on numerical thresholds of individual risk factors, to determine treatment strategies.

  7. Gemfibrozil, stretching arms beyond lipid lowering

    PubMed Central

    Roy, Avik; Pahan, Kalipada

    2009-01-01

    Gemfibrozil is long known for its ability to reduce the level of triglycerides in the blood circulation and to decrease the risk of hyperlipidemia. However, a number of recent studies reveal that apart from its lipid-lowering effects, gemfibrozil can also regulate many other signaling pathways responsible for inflammation, switching of T-helper cells, cell-to-cell contact, migration, and oxidative stress. In this review, we have made an honest attempt to analyze various biological activities of gemfibrozil and associated mechanisms that may help to consider this drug for different human disorders as primary or adjunct therapy. PMID:19694602

  8. Real-world effectiveness of lipid-lowering therapy in male and female outpatients with coronary heart disease: relation to pre-treatment low-density lipoprotein-cholesterol, pre-treatment coronary heart disease risk, and other factors.

    PubMed

    Krobot, Karl J; Yin, Donald D; Alemao, Evo; Steinhagen-Thiessen, Elisabeth

    2005-02-01

    Determinants of the real-world effectiveness of lipid-lowering therapy have been rarely assessed in an unselected observational coronary heart disease (CHD) community cohort over time. Randomly drawn patients (n=605) from randomly drawn practices (n=62) were retrospectively followed for a median of 3.6 years (1998-2002) on lipid-lowering therapy (98% statins). Coronary heart disease population-averaged estimates and variances accounting for repeated measurements within patients were obtained using generalized estimating equations. Post-treatment low-density lipoprotein-cholesterol (LDL-C) was 124 mg/dl in men and 141 mg/dl in women and was independently associated (all P<0.05) with pre-treatment LDL-C (+3.7 mg/dl per 10 mg/dl increment), female sex (+14.0 mg/dl), coronary bypass (-9.5 mg/dl), drug-treated diabetes mellitus (-6.8 mg/dl), and era 2002/2001 versus 1999/2000 (-6.4 mg/dl) in age-adjusted multivariate analyses. Holding pre-treatment LDL-C constant post-treatment LDL-C was associated with pre-treatment Framingham CHD risk in men (-13.9 mg/dl per doubling of risk), whereas LDL-C control in women resembled that in low-risk men. The likelihood of attaining LDL-C <100 mg/dl was 0.28 in men and 0.17 in women and was likewise associated with the above factors. Low-density lipoprotein-cholesterol control remained low despite lipid-lowering therapy across a wide range of pre-treatment LDL-C and pre-treatment CHD risk. Low-density lipoprotein-cholesterol control in women was inferior to that in men, a finding that warrants attention and clarification.

  9. Overprescribing of lipid lowering agents.

    PubMed

    Smith, M A; Cox, E D; Bartell, J M

    2006-08-01

    Undertreatment of hyperlipidemia has received considerable attention. However, little is known about trends in overprescribing of lipid lowering agents. We examined these trends and their associations with physician, practice, and organisational factors. 2034 physicians were surveyed twice: baseline (1996-7) and follow up (1998-9). On each occasion they were asked: "For what percentage of 50 year old men without other cardiac risk factors would you recommend an oral agent for total cholesterol of 240, LDL 150, and HDL 50 after 6 months on a low cholesterol diet?" During the survey period the National Cholesterol Education Program guidelines did not recommend prescribing for these patients. Binomial and multinomial logistic regressions assessed baseline overprescribing and longitudinal changes in overprescribing, accounting for complex sampling. 39% of physicians recommended prescribing at baseline (round 1), increasing at follow up (round 2) to 51% (p < 0.001). Physicians who were more likely to overprescribe at baseline were less likely to be board certified (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.38 to 0.63; p < 0.001), were in solo or two-physician practices (OR 1.88, 95% CI 1.46 to 2.41; p < 0.001), had more revenue from Medicare (OR 1.10, 95% CI 1.03 to 1.17; p = 0.004) or Medicaid (OR 1.09, 95% CI 1.01 to 1.18; p = 0.03), or were family physicians (OR 1.87, 95% CI 1.35 to 2.58; p < 0.001). Physicians with large increases in overprescibing were more likely than those with small increases in overprescribing to be international medical graduates (OR 2.09, 95% CI 1.20 to 3.64; p = 0.011) and to spend more hours in patient care (OR 1.14, 95% CI 1.03 to 1.26; p = 0.016). Overprescribing of lipid lowering agents is commonplace and increased. At baseline and longitudinally, overprescribing was primarily associated with physician and practice characteristics and not with organisational factors.

  10. Overprescribing of lipid lowering agents

    PubMed Central

    Smith, M A; Cox, E D; Bartell, J M

    2006-01-01

    Background Undertreatment of hyperlipidemia has received considerable attention. However, little is known about trends in overprescribing of lipid lowering agents. We examined these trends and their associations with physician, practice, and organisational factors. Methods 2034 physicians were surveyed twice: baseline (1996–7) and follow up (1998–9). On each occasion they were asked: “For what percentage of 50 year old men without other cardiac risk factors would you recommend an oral agent for total cholesterol of 240, LDL 150, and HDL 50 after 6 months on a low cholesterol diet?” During the survey period the National Cholesterol Education Program guidelines did not recommend prescribing for these patients. Binomial and multinomial logistic regressions assessed baseline overprescribing and longitudinal changes in overprescribing, accounting for complex sampling. Results 39% of physicians recommended prescribing at baseline (round 1), increasing at follow up (round 2) to 51% (p<0.001). Physicians who were more likely to overprescribe at baseline were less likely to be board certified (odds ratio (OR) 0.49, 95% confidence interval (CI) 0.38 to 0.63; p<0.001), were in solo or two‐physician practices (OR 1.88, 95% CI 1.46 to 2.41; p<0.001), had more revenue from Medicare (OR 1.10, 95% CI 1.03 to 1.17; p = 0.004) or Medicaid (OR 1.09, 95% CI 1.01 to 1.18; p = 0.03), or were family physicians (OR 1.87, 95% CI 1.35 to 2.58; p<0.001). Physicians with large increases in overprescibing were more likely than those with small increases in overprescribing to be international medical graduates (OR 2.09, 95% CI 1.20 to 3.64; p = 0.011) and to spend more hours in patient care (OR 1.14, 95% CI 1.03 to 1.26; p = 0.016). Conclusions Overprescribing of lipid lowering agents is commonplace and increased. At baseline and longitudinally, overprescribing was primarily associated with physician and practice characteristics and not with organisational factors

  11. Neoatherosclerosis causing occlusive in-stent restenosis: Impact of intracoronary imaging in the intensity of lipid-lowering therapy.

    PubMed

    Martí, David; López, Edurne; Álvarez, Salvador; Palazuelos, Jorge; Rada, Ignacio; Alfonso, Fernando

    2016-12-01

    The unique physical properties of optical coherence tomography (OCT) make it a useful technique in the study of restenosis mechanisms. In fact, OCT is able to differentiate between neointimal proliferation and neoatherosclerosis within the stent. We report a rare case of occlusive neoatherosclerosis presenting beyond one year after a successful drug-eluting stent implantation. The impact of OCT findings in the clinical decision making process is emphasized.

  12. Status of lipid-lowering therapy prescribedbased on recommendations in the 2002 report of the Japan Atherosclerosis Society Guideline for Diagnosis and Treatment of Hyperlipidemia in Japanese Adults: A study of the Japan Lipid Assessment Program (J-LAP).

    PubMed

    Teramoto, Tamio; Kashiwagi, Atsunori; Mabuchi, Hiroshi; J-Lap Investigators

    2005-03-01

    In its 1997 Guideline for Diagnosis and Treatment of Hyperlipidemia in Japanese Adults and subsequent revisions, the Japan10 Atherosclerosis Society (JAS) recommends serum lipid management goals (SLMGs) based on a coronary heart disease (CHD) risk classification. A literature search revealed that the status of lipid-lowering therapy based on the current JAS recommendations in Japan has not been assessed. The aim of this study was to evaluate the efficacy of current lipid-lowering 10 regimens, and to provide the best possible therapeutic strategies for patients with hyperlipidemia by identifying risk factors for the development of CHD, based on the current JAS recommendations. This multicenter, retrospective study was conducted using data 10 from patients under the care of physicians at 12,500 randomly selected institutions across Japan. Physicians received a survey concerning lipid-lowering therapy, on which each physician provided data from 10 consecutive adult patients with hyperlipidemia who had been prescribed lipid-lowering therapy for at least 3 months before the survey was administered, and who were undergoing routine follow-up on an outpatient basis. Physicians provided patients' demographic and clinical data, including JAS-defined CHD risk classification coronary risk factors and pre- and posttreatment (after ≥3 months) serum lipid levels, and the types and dosages of drugs in patients' current and prior treatment regimens. These data were used to assess the efficacy of lipid-lowering regimens and rates of patients achieving the SLMGs recommended by the JAS. A total of 2540 physicians participated in the survey, and data from 10 24,893 Japanese patients (mean [SD] age, 65.8 [10.5] years) with hyperlipidemia were included in the study. Patients with familial hyperlipidemia (845/24,893 [3.4%]) were excluded from most of the analyses, leaving 24,048 patients with primary hyperlipidemia. The most prevalent coronary risk factors included age (21,902 [91

  13. The use of lipid-lowering therapy and effects of antihyperglycaemic therapy on lipids in subjects with type 2 diabetes with or without cardiovascular disease: a pooled analysis of data from eleven randomized trials with insulin glargine 100 U/mL.

    PubMed

    Hanefeld, Markolf; Traylor, Louise; Gao, Ling; Landgraf, Wolfgang

    2017-05-19

    Dyslipidaemia is a major contributor to the increased risk of cardiovascular disease (CVD) associated with type 2 diabetes (T2D). This study aimed to characterize the extent of lipid-lowering therapy use and its impact on lipid and glycaemic outcomes in people with T2D uncontrolled on oral agents who were enrolled in insulin glargine 100 units/mL (Gla-100) randomized controlled trials (RCTs). A post hoc patient-level pooled analysis of eleven RCTs (≥24 weeks' duration) comparing Gla-100 (±oral antidiabetes drugs [OADs]) with OADs alone in people with T2D was performed. Baseline and Week 24 or study endpoint lipid status (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], non-high-density lipoprotein cholesterol [non-HDL-C] and triglycerides) and indices of glycaemic control (glycosylated haemoglobin, fasting plasma glucose [FPG]) were examined in patient groups according to treatment received and CVD status. Lipid-lowering therapy was provided at the discretion of physicians at baseline and throughout the studies. Of the 4768 participants included in the analysis, 41% (n = 1940) received lipid-lowering therapy. Only 51% of participants with CVD (1885/3672) were treated with lipid-lowering therapy; these participants had significantly lower levels of LDL-C, HDL-C and non-HDL-C, and higher levels of triglycerides versus patients not treated with lipid-lowering therapy at baseline and study endpoint (P < 0.001 for all). Antihyperglycaemia therapy resulted in decreases in glycosylated haemoglobin (-1.4 to -1.6%) and FPG (-68.9 to -75.3 mg/dL) at Week 24. Furthermore, slight improvements in non-HDL-C (-3.9 to -9.1 mg/dL) and triglyceride levels (-25.8 to -51.2 mg/dL) were observed. Similar changes were seen irrespective of lipid-lowering therapy or CVD status. In a T2D cohort included in Gla-100 clinical studies, many participants with T2D and CVD did not receive lipid-lowering therapy, and for most categories of lipid

  14. Effectiveness of adherence to lipid lowering therapy on LDL-cholesterol in patients with very high cardiovascular risk: A real-world evidence study in primary care.

    PubMed

    Guglielmi, Valeria; Bellia, Alfonso; Pecchioli, Serena; Della-Morte, David; Parretti, Damiano; Cricelli, Iacopo; Medea, Gerardo; Sbraccia, Paolo; Lauro, Davide; Cricelli, Claudio; Lapi, Francesco

    2017-08-01

    Despite management guidelines advocating statin/ezetimibe use in very high cardiovascular risk (CV) conditions, adherence to this therapy is still suboptimal and LDL-C target attainment unsatisfactory. We aimed to investigate the level of adherence to statin/ezetimibe and LDL-C target achievement rates in an unselected very high CV risk population in primary care setting in Italy. We performed a retrospective population-based study using the Health Search IMS Health Longitudinal Patient Database (HSD), including adult patients at very high CV risk, newly treated with statin, ezetimibe or their combination, with 3 and 6 months of follow-up. Although the large majority of patients had previous major CV events (99.9%), only 61% and 55.14% resulted adherent (Proportion of Days Covered, PDC≥80%) after 3 and 6 months, respectively. High adherence entailed almost a three times higher probability to reach the therapeutic LDL-C target (3 months: OR = 2.26 [95% [CI]: 1.88 to 2.72]; 6-months: OR = 2.74 [95% CI: 2.27 to 3.31]). The odds to treat to LDL-C target was greater for simvastatin-ezetimibe fixed combination, simvastatin, atorvastatin and rosuvastatin, in decreasing order. Finally, poor adherence was slightly more prevalent among patients treated with less effective statins, and at both low and maximal dosage regimens. This population-based study showed that adherence to statin therapy is poor even among patients who have already experienced a CV event. Failure to achieve recommended LDL-C levels appears imputable to the use of moderate doses and low to standard efficacy statins. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Switching from high-efficacy lipid-lowering therapies to simvastatin and low-density lipoprotein cholesterol goal attainment in coronary heart disease/coronary heart disease-equivalent patients.

    PubMed

    Tunceli, Kaan; Sajjan, Shiva G; Ramey, Dena R; Neff, David R; Tershakovec, Andrew M; Hu, X Henry; Tomassini, Joanne E; Foody, Joanne M

    2010-01-01

    The availability of generic simvastatin in 2006 has prompted substantial changes in formulary recommendations for lipid-management agents. To assess the impact of switches from high-efficacy lipid-lowering therapy to simvastatin on low-density lipoprotein cholesterol (LDL-C) and goal attainment in coronary heart disease (CHD) or CHD risk-equivalent patients in a managed care setting. In this retrospective observational study, we estimated the least squares mean difference in the percent change from baseline LDL-C and the odds ratios for LDL-C goal attainment rates (<100 mg/dL and <70 mg/dL) at follow-up for each baseline high-efficacy lipid-lowering therapy with the analysis of covariance and logistic regressions, respectively. We identified 18,061 patients who, between September 1, 2004 and October 31, 2008, were either switched from or remained on their initial high-efficacy LDL-C lowering therapy: ezetimibe/simvastatin fixed-dose combination (E/S), rosuvastatin, or atorvastatin. The difference in percent change in LDL-C levels from baseline were 25.2 (95% confidence interval 21.2-29.2), 13.0 (6.0-20.0), and 3.1 (0.3-5.9) greater in switchers to simvastatin in the E/S, rosuvastatin, and atorvastatin comparisons, respectively, after adjusting for age, sex, and starting dose of the initial therapy. For switchers, the percent of patients at LDL-C <100 mg/dL at follow-up decreased from 83.5% to 63.8% in the E/S, 67.7% to 52.7% in the rosuvastatin, and 65.1% to 60.2% in the atorvastatin cohorts. The percent of patients at LDL-C <70 mg/dL at follow-up was lower for all switcher groups compared with nonswitchers. Among CHD/CHD risk-equivalent patients, switching to simvastatin was associated with increases in LDL-C levels and lower LDL-C goal attainment rates. The public health impact of this phenomenon on population risk and CHD events remains to be determined. Copyright © 2010 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  16. Intensity modulated proton therapy

    PubMed Central

    Grassberger, C

    2015-01-01

    Intensity modulated proton therapy (IMPT) implies the electromagnetic spatial control of well-circumscribed “pencil beams” of protons of variable energy and intensity. Proton pencil beams take advantage of the charged-particle Bragg peak—the characteristic peak of dose at the end of range—combined with the modulation of pencil beam variables to create target-local modulations in dose that achieves the dose objectives. IMPT improves on X-ray intensity modulated beams (intensity modulated radiotherapy or volumetric modulated arc therapy) with dose modulation along the beam axis as well as lateral, in-field, dose modulation. The clinical practice of IMPT further improves the healthy tissue vs target dose differential in comparison with X-rays and thus allows increased target dose with dose reduction elsewhere. In addition, heavy-charged-particle beams allow for the modulation of biological effects, which is of active interest in combination with dose “painting” within a target. The clinical utilization of IMPT is actively pursued but technical, physical and clinical questions remain. Technical questions pertain to control processes for manipulating pencil beams from the creation of the proton beam to delivery within the patient within the accuracy requirement. Physical questions pertain to the interplay between the proton penetration and variations between planned and actual patient anatomical representation and the intrinsic uncertainty in tissue stopping powers (the measure of energy loss per unit distance). Clinical questions remain concerning the impact and management of the technical and physical questions within the context of the daily treatment delivery, the clinical benefit of IMPT and the biological response differential compared with X-rays against which clinical benefit will be judged. It is expected that IMPT will replace other modes of proton field delivery. Proton radiotherapy, since its first practice 50 years ago, always required the

  17. Rationale for aggressive lipid lowering in high-risk patients.

    PubMed

    Cohen, Jerome D

    2011-04-01

    According to current guidelines from the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III), the target low-density lipoprotein cholesterol (LDL-C) level for patients with established coronary heart disease (CHD) or CHD risk equivalents is less than 100 mg/dL, with an optional target of less than 70 mg/dL. More recent data suggest, however, that the physiologically normal level of LDL-C and the level at which atherogenesis is initiated is much lower. Overall, the data convincingly demonstrate that LDL-C lowering is associated with a significant reduction in CHD events, regardless of preexisting CHD. The NCEP ATP III treatment guidelines, published in 2002 and updated in 2004, do not reflect more recent findings on intensive lipid-lowering therapy, which are likely be addressed in the NCEP ATP IV guidelines, scheduled to be released in 2011. Drug options for LDL-C lowering include statins (the drug of choice), bile acid sequestrants, nicotinic acid, fibrates, and selective cholesterol absorption inhibitors.

  18. Patterns and predictors of lipid-lowering therapy in patients with atherosclerotic cardiovascular disease and/or diabetes mellitus in 2014: Insights from a large US managed-care population.

    PubMed

    Steen, Dylan L; Khan, Irfan; Becker, Laura; Foody, JoAnne M; Gorcyca, Katherine; Sanchez, Robert J; Giugliano, Robert P

    2017-03-01

    Lowering low-density lipoprotein cholesterol with statins reduces risk of cardiovascular events. We examined patterns and predictors of filled prescriptions for lipid-lowering therapy (LLT) in subgroups of patients with atherosclerotic cardiovascular disease (ASCVD) and/or diabetes mellitus (DM). Statin treatment remains underutilized across subgroups of high CV risk patients. Patients in the Optum Research Database with these criteria were included: age ≥20 years, 2 years continuous enrollment, and ASCVD and/or DM. Patients were hierarchically classified by the presence of recent acute coronary syndrome, other coronary heart disease, ischemic stroke, peripheral arterial disease (PAD), or only DM. Predictors of filled LLT regimens were examined using multinomial logistic regression. A total of 1 055 932 individuals met all inclusion criteria. Evidence by point-in-time analysis of filled (not only written) statin prescriptions was 45% for the overall cohort. By subgroups, this was 62%, 52%, 43%, 36%, and 40% for recent acute coronary syndrome, other coronary heart disease, ischemic stroke, PAD, and only DM, respectively. Predictors of higher rates of any statin regimen included age 50 to 69 years, male sex, absence of comorbidities, and filled prescriptions of other standard-of-care therapies. In 2014, only 49% of patients with ASCVD and 40% with only DM had evidence for a filled statin prescription. Those with indications of ischemic stroke, PAD, and DM were less likely to receive statins than those with coronary conditions. Other characteristics such as advanced age, female sex, and noncardiac conditions predicted less statin utilization, thereby representing good targets for quality improvement. © 2016 Wiley Periodicals, Inc.

  19. Coumarin and Derivates as Lipid Lowering Agents.

    PubMed

    Tejada, Silvia; Martorell, Miquel; Capo, Xavier; Tur, Josep A; Pons, Antoni; Sureda, Antoni

    2017-01-01

    Cardiovascular disease is the main cause of death in the developed countries. Dyslipidaemia is one of the risk factors associated to cardiovascular disease and it is characterised by abnormal amounts of lipids (i.e. cholesterol and fatty acids) and/or circulating lipoproteins in the blood. Oxidative stress has been implicated in the pathogenesis of various illnesses including cardiovascular disease. In this way, the potential therapeutic or preventive effects of antioxidant mediators have recently drawn much attention. Coumarin (1,2-benzopyrone) is a natural phenolic compound found in many plants such as citrus fruits, tomatoes, vegetables and green tea. Coumarin and derivates are proposed as lipid lowering agents due to its broad pharmacological activities, mainly the implicated in vasodilator and antioxidant effect. Several studies have evidenced a promising role of coumarin and several of its derivates as lipid lowering agents. In the current work, the available reports related to the promising function of these compounds are reviewed.

  20. Efficacy and safety of alirocumab in patients with hypercholesterolemia not adequately controlled with non-statin lipid-lowering therapy or the lowest strength of statin: ODYSSEY NIPPON study design and rationale.

    PubMed

    Teramoto, Tamio; Kondo, Akira; Kiyosue, Arihiro; Harada-Shiba, Mariko; Ishigaki, Yasushi; Tobita, Kimimasa; Kawabata, Yumiko; Ozaki, Asuka; Baccara-Dinet, Marie T; Sata, Masataka

    2017-06-17

    Statins are generally well-tolerated and serious side effects are infrequent, but some patients experience adverse events and reduce their statin dose or discontinue treatment altogether. Alirocumab is a highly specific, fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), which can produce substantial and sustained reductions of low-density lipoprotein cholesterol (LDL-C). The randomized, double-blind, placebo-controlled, parallel-group, phase 3 ODYSSEY NIPPON study will explore alirocumab 150 mg every 4 weeks (Q4W) in 163 Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin (5 mg/day) or are receiving a non-statin lipid-lowering therapy (LLT) (fenofibrate, bezafibrate, ezetimibe, or diet therapy alone). Hypercholesterolemia is defined as LDL-C ≥ 100 mg/dL (2.6 mmol/L) in patients with heterozygous familial hypercholesterolemia or non-familial hypercholesterolemia with a history of documented coronary heart disease, or ≥120 mg/dL (3.1 mmol/L) in patients with non-familial hypercholesterolemia classified as primary prevention category III (i.e. high-risk patients). During the 12-week double-blind treatment period, patients will be randomized (1:1:1) to receive alirocumab subcutaneously (SC) 150 mg Q4W alternating with placebo for alirocumab Q4W, or alirocumab 150 mg SC every 2 weeks (Q2W), or SC placebo Q2W. The primary efficacy endpoint is the percentage change in calculated LDL-C from baseline to week 12. The long-term safety and tolerability of alirocumab will also be investigated. The ODYSSEY NIPPON study will provide insights into the efficacy and safety of alirocumab 150 mg Q4W or 150 mg Q2W among Japanese patients with hypercholesterolemia who are on the lowest-strength dose of atorvastatin, or are receiving a non-statin LLT (including diet therapy alone). ClinicalTrials.gov number: NCT02584504.

  1. Intensity-Modulated Radiation Therapy (IMRT)

    MedlinePlus

    ... Resources Professions Site Index A-Z Intensity-Modulated Radiation Therapy (IMRT) Intensity-modulated radiotherapy (IMRT) uses linear ... and after this procedure? What is Intensity-Modulated Radiation Therapy and how is it used? Intensity-modulated ...

  2. [Lipid-lowering drugs and PCSK9].

    PubMed

    Millán Núñez-Cortés, Jesús; Mostaza Prieto, José M

    2016-05-01

    PCSK9 is a protease, synthesized mainly in the liver, which promotes the hepatic degradation of the LDL receptor and consequently decreases LDL receptor density and clearance of LDL particles. Statins inhibit HMG-CoA-reductase activity, an enzyme that catalyses an important step in hepatic cholesterol biosynthesis. The decrease of the hepatic intracellular cholesterol pool produced by these drugs upregulates the activity of the SREBP2 transcription factor, which subsequently stimulates the expression of the LDL receptor gene, an effect that is followed by an increase in the serum concentration of PCSK9. This article aims to review the effects of different lipid-lowering drugs on plasma PCSK9 concentrations. Overall, statins increase blood PCSK9 levels, an effect that is enhanced by ezetimibe. In contrast, others drugs, such as fibrates and niacin, could decrease PCSK9 levels.

  3. Role of phytosterols in lipid-lowering: current perspectives.

    PubMed

    Gupta, A K; Savopoulos, C G; Ahuja, J; Hatzitolios, A I

    2011-04-01

    The cholesterol-lowering effect of plant sterols was first discovered in the early 1950s. However, it is only recently that plant sterols have become clinically important, when advances in food-technology have made it possible to combine sterols with a variety of food products including margarines, yogurts, fruit juices and cereal bars. We review the clinical trial evidence of lipid-lowering efficacy of plant sterols and discuss their implications in routine clinical practice. To generate the evidence we searched the Pubmed database for English language literature, using relevant keywords and medical subject heading (MeSH) terms, and extracted the findings from recently published studies and meta-analyses on this topic. Our findings suggest that the short-term use of food supplements rich in plant sterols is a safe and effective strategy; to maximize the benefits of dietary and lifestyle therapy, either with or without statin therapy, among majority of dyslipidemic patients with need for additional lipid-lowering.

  4. Lipid-lowering update 2001. Aggressive new goals.

    PubMed Central

    Fenske, T. K.

    2001-01-01

    OBJECTIVE: To review the central role of cholesterol in coronary artery disease (CAD), underscore the need for identifying patients at high risk of CAD, and discuss treatment of dyslipidemias. QUALITY OF EVIDENCE: Current literature (1995-2000) was searched via MEDLINE using the MeSH headings "cholesterol," "risk reduction," and "statins." Recommendations in this paper are based mainly on the results of large randomized controlled trials. Preference was given to more recent articles, clinically relevant articles, and landmark clinical trials. MAIN MESSAGE: Lipid lowering, and specifically low-density lipoprotein lowering, has been repeatedly shown in large clinical trials to improve survival dramatically and reduce cardiac events in both primary and secondary prevention. Identifying those at highest risk for future cardiac events is critical because these patients will benefit most from aggressive modification of risk factors. The definition of high risk has been expanded to include patients with diabetes mellitus and peripheral vascular disease, as well as those with established CAD. A full lipid profile is required for these patients to assess risk and develop a lipid-lowering strategy with proven effectiveness. CONCLUSION: With the advent of powerful, efficacious, and well tolerated cholesterol-modifying therapies, lipid normalization should be a mandate for all physicians caring for patients with established CAD and patients at risk of developing CAD. PMID:11228031

  5. Intensive Insulin Therapy: Tight Blood Sugar Control

    MedlinePlus

    ... insulin therapy can help you achieve desired blood sugar control and what intensive insulin therapy requires of ... aggressive treatment approach designed to control your blood sugar levels. Intensive insulin therapy requires close monitoring of ...

  6. High-dose statin therapy with rosuvastatin reduces small dense LDL and MDA-LDL: The Standard versus high-dose therApy with Rosuvastatin for lipiD lowering (SARD) trial.

    PubMed

    Nishikido, Toshiyuki; Oyama, Jun-Ichi; Keida, Takehiko; Ohira, Hiroshi; Node, Koichi

    2016-04-01

    Cardiovascular events (CV) continue to occur due to residual risks in high-risk patients in spite of substantial reductions in the low-density lipoprotein cholesterol (LDL) with statins. It has been reported that the small-dense LDL (sd-LDL) components of high atherogenic particles are associated with an increased risk of CV, more than large buoyant LDL. However, there are few reports regarding the effects of high-dose statin therapy in improving atherogenic lipoproteins. In this prospective, randomized, open-label, multicenter study, a total of 111 high-risk patients were randomly assigned to two groups. In the high-dose therapy group, 58 patients were administered 5mg of rosuvastatin per day for four weeks, after which the dose was titrated to 10mg for the following eight weeks. In the low-dose therapy group, 53 patients were given 2.5mg for 12 weeks. We evaluated the lipid profiles, including the levels of sd-LDL, malondialdehyde-modified LDL-cholesterol (C) (MDA-LDL) as oxidized-LDL, and remnant-like particle-cholesterol. The LDL-C, non-high-density lipoprotein (HDL), and LDL-C/HDL-C ratio were decreased in the high-dose therapy group (p<0.01). Moreover, the sd-LDL and MDA-LDL levels were significantly reduced in the high-dose therapy group (p<0.05). There were no serious adverse events in either group. High-dose statin therapy significantly reduced the sd-LDL and MDA-LDL components of atherosclerotic lipoproteins without adverse events in comparison with low-dose statin therapy. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  7. Intensity-modulated radiation therapy.

    PubMed

    Goffman, Thomas E; Glatstein, Eli

    2002-07-01

    Intensity-modulated radiation therapy (IMRT) is an increasingly popular technical means of tightly focusing the radiation dose around a cancer. As with stereotactic radiotherapy, IMRT uses multiple fields and angles to converge on the target. The potential for total dose escalation and for escalation of daily fraction size to the gross cancer is exciting. The excitement, however, has greatly overshadowed a range of radiobiological and clinical concerns.

  8. Effect of intensive lipid-lowering therapy with rosuvastatin on progression of carotid intima-media thickness in Japanese patients: Justification for Atherosclerosis Regression Treatment (JART) study.

    PubMed

    Nohara, Ryuji; Daida, Hiroyuki; Hata, Mitsumasa; Kaku, Kohei; Kawamori, Ryuzo; Kishimoto, Junji; Kurabayashi, Masahiko; Masuda, Izuru; Sakuma, Ichiro; Yamazaki, Tsutomu; Yokoi, Hiroyoshi; Yoshida, Masayuki

    2012-01-01

    A recent trial in Western countries has shown that rosuvastatin slows progression of carotid intima-media thickness (IMT) in patients with modest carotid IMT thickening and elevated levels of low-density lipoprotein cholesterol (LDL-C). We conducted a prospective, randomized, open-label, blinded-endpoint trial to determine whether rosuvastatin is more effective than pravastatin in slowing progression of carotid IMT in Japanese patients. Adult patients with hypercholesterolemia who had a maximum IMT ≥1.1mm were randomly assigned to receive rosuvastatin or pravastatin. The primary endpoint was the percent change in the mean-IMT, which was measured by a single observer who was blinded to the treatment assignments. The trial was stopped on April 2011 according to the recommendation by the data and safety monitoring committee. A total of 348 patients (173 rosuvastatin; 175 pravastatin) were enrolled and 314 (159 rosuvastatin; 155 pravastatin) were included in the primary analysis. Mean (SD) percentage changes in the mean-IMT at 12 months were 1.91% (10.9) in the rosuvastatin group and 5.8% (12.0) in the pravastatin group, with a difference of 3.89% (11.5) between the groups (P=0.004). At 12 months, 85 patients (59.4%) in the rosuvastatin group achieved a LDL-C/high-density lipoprotein cholesterol ratio ≤1.5 compared with 24 patients (16.4%) in the pravastatin group (P<0.0001). Rosuvastatin significantly slowed progression of carotid IMT at 12 months compared with pravastatin.

  9. Lipid-Lowering Pharmaceutical Clofibrate Inhibits Human Sweet Taste.

    PubMed

    Kochem, Matthew; Breslin, Paul A S

    2017-01-01

    T1R2-T1R3 is a heteromeric receptor that binds sugars, high potency sweeteners, and sweet taste blockers. In rodents, T1R2-T1R3 is largely responsible for transducing sweet taste perception. T1R2-T1R3 is also expressed in non-taste tissues, and a growing body of evidence suggests that it helps regulate glucose and lipid metabolism. It was previously shown that clofibric acid, a blood lipid-lowering drug, binds T1R2-T1R3 and inhibits its activity in vitro The purpose of this study was to determine whether clofibric acid inhibits sweetness perception in humans and is, therefore, a T1R2-T1R3 antagonist in vivo Fourteen participants rated the sweetness intensity of 4 sweeteners (sucrose, sucralose, Na cyclamate, acesulfame K) across a broad range of concentrations. Each sweetener was prepared in solution neat and in mixture with either clofibric acid or lactisole. Clofibric acid inhibited sweetness of every sweetener. Consistent with competitive binding, inhibition by clofibric acid was diminished with increasing sweetener concentration. This study provides in vivo evidence that the lipid-lowering drug clofibric acid inhibits sweetness perception and is, therefore, a T1R carbohydrate receptor inhibitor. Our results are consistent with previous in vitro findings. Given that T1R2-T1R3 may in part regulate glucose and lipid metabolism, future studies should investigate the metabolic effects of T1R inhibition. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. New Era of Lipid-Lowering Drugs

    PubMed Central

    Rye, Kerry-Anne

    2016-01-01

    There are several established lipid-modifying agents, including statins, fibrates, niacin, and ezetimibe, that have been shown in randomized clinical outcome trials to reduce the risk of having an atherosclerotic cardiovascular event. However, in many people, the risk of having an event remains unacceptably high despite treatment with these established agents. This has stimulated the search for new therapies designed to reduce residual cardiovascular risk. New approaches that target atherogenic lipoproteins include: 1) inhibition of proprotein convertase subtilisin/kexin type 9 to increase removal of atherogenic lipoproteins from plasma; 2) inhibition of the synthesis of apolipoprotein (apo) B, the main protein component of atherogenic lipoproteins; 3) inhibition of microsomal triglyceride transfer protein to block the formation of atherogenic lipoproteins; 4) inhibition of adenosine triphosphate citrate lyase to inhibit the synthesis of cholesterol; 5) inhibition of the synthesis of lipoprotein(a), a factor known to cause atherosclerosis; 6) inhibition of apoC-III to reduce triglyceride-rich lipoproteins and to enhance high-density lipoprotein (HDL) functionality; and 7) inhibition of cholesteryl ester transfer protein, which not only reduces the concentration of atherogenic lipoproteins but also increases the level and function of the potentially antiatherogenic HDL fraction. Other new therapies that specifically target HDLs include infusions of reconstituted HDLs, HDL delipidation, and infusions of apoA-I mimetic peptides that mimic some of the functions of HDLs. This review describes the scientific basis and rationale for developing these new therapies and provides a brief summary of established therapies. PMID:26983688

  11. Prevention of cardiovascular disease based on lipid lowering treatment: a challenge for the Mexican health system.

    PubMed

    Gómez-Pérez, Francisco J; Rojas, Rosalba; Villalpando, Salvador; Barquera, Simón; Rull, Juan; Aguilar-Salinas, Carlos A

    2010-01-01

    To estimate the percentage of Mexican adults that may require lipid-lowering treatment according to National Cholesterol Education Program-III guidelines, using data from the National Health and Nutrition Survey 2006 (ENSANut 2006). Information was obtained from 4 040 subjects aged 20 to 69 years, studied after a 9 to 12 hours fast. A cardiovascular risk equivalent was found in 13.8% and >or=2 risk factors were present in 31.5% of the population. LDL-C concentrations were above the treatment goal in 70% of the high-risk group and in 38.6% of subjects with >or=2 risk factors. Nearly 12 million Mexicans should be taught how to change their lifestyles and close to 8 million individuals require drug therapy to decrease their cardiovascular risk. Thirty percent of Mexican adults require some form of lipid-lowering treatment (lifestyle modifications in 36.25%, drug therapy in 24.19%).

  12. Changes in Use of Lipid Lowering Medications among Black and White Dual Enrollees with Diabetes Transitioning from Medicaid to Medicare Part D Drug Coverage

    PubMed Central

    Adams, Alyce S.; Madden, Jeanne M.; Zhang, Fang; Soumerai, Stephen B.; Gilden, Dan; Griggs, Jennifer; Trinacty, Connie Mah; Bishop, Christine; Ross-Degnan, Dennis

    2014-01-01

    Background The use of lipid lowering agents is suboptimal among dual enrollees, particularly blacks. Objectives To determine whether the removal of restrictive drug caps under Medicare Part D reduced racial differences among dual enrollees with diabetes. Research Design An interrupted time series with comparison series design (ITS) cohort study. Subjects 8,895 black and white diabetes ≥18 year old patients drawn from a nationally representative sample of fee-for-service dual enrollees (January 2004–December 2007) in states with and without drug caps before Part D. Measures We examined the monthly (1) proportion of patients with any use of lipid lowering therapies and (2) intensity of use. Stratification measures included age (<65, ≥65), race (white vs. black) and gender. Results At baseline, lipid lowering drug use was higher in no drug cap states (drug cap: 54.0% vs. non-drug cap: 66.8%) and among whites versus blacks (drug cap: 58.5% vs. 44.9%, no drug cap: 68.4% vs. 61.9%). In strict drug cap states only, Part D was associated with an increase in the proportion with any use [nonelderly: +0.07 absolute percentage points (95% CI: 0.06, 0.09), p<0.001; elderly: +0.08 (0.06,0.10), p<0.001] regardless of race. However, we found no evidence of a change in the white-black gap in the proportion of users despite the removal of a significant financial barrier. Conclusions Medicare Part D was associated with increased use of lipid lowering drugs, but racial gaps persisted. Understanding non-coverage-related barriers is critical to maximizing the potential benefits of coverage expansions for disparities reduction. PMID:24988304

  13. Intensive insulin therapy in the intensive cardiac care unit.

    PubMed

    Hasin, Tal; Eldor, Roy; Hammerman, Haim

    2006-01-01

    Treatment in the intensive cardiac care unit (ICCU) enables rigorous control of vital parameters such as heart rate, blood pressure, body temperature, oxygen saturation, serum electrolyte levels, urine output and many others. The importance of controlling the metabolic status of the acute cardiac patient and specifically the level of serum glucose was recently put in focus but is still underscored. This review aims to explain the rationale for providing intensive control of serum glucose levels in the ICCU, especially using intensive insulin therapy and summarizes the available clinical evidence suggesting its effectiveness.

  14. The clinical and nutritional implications of lipid-lowering drugs that act in the gastrointestinal tract.

    PubMed

    Sullivan, David R

    2005-02-01

    A new class of cholesterol-lowering therapy that reduces intestinal sterol absorption has recently been introduced. This increases the number of classes of lipid-lowering agents that directly affect gastrointestinal function and raises questions concerning the overall effect of these agents on absorption and nutritional status. A recent assessment notes a paucity of information concerning the factors that affect the bioavailability and intestinal absorption of lipophilic nutrients. By contrast, the specificity of the mechanisms of action of new drugs acting on the gastrointestinal tract may circumvent some of the detrimental effects on nutrient and drug bioavailability that have been noted with older forms of treatment. The clinical imperative for aggressive control of lipid and metabolic risk factors makes widespread use, alone or in combination, of lipid-lowering agents that affect the gastrointestinal tract seem increasingly likely. Whilst the opportunity for therapeutic synergy is attractive, care will be required to avoid interference with intestinal absorptive function.

  15. Nutraceuticals in lipid-lowering treatment: a narrative review on the role of chitosan.

    PubMed

    Patti, Angelo Maria; Katsiki, Niki; Nikolic, Dragana; Al-Rasadi, Khalid; Rizzo, Manfredi

    2015-05-01

    Lipid-lowering drugs may cause adverse effects and, although lipid targets may be achieved, a substantial residual cardiovascular (CV) risk remains. Treatment with agents mimicking proteins present in the body, such as incretin-based therapies, provided promising results. However, in order to improve lipids and CV risk, lifestyle measures remain important. Some researchers focused on nutraceuticals that may beneficially affect metabolic parameters and minimize CV risk. Chitosan, a dietary fiber, can regulate lipids with benefit on anthropometric parameters. The beneficial properties of dietary supplements (such as green tea extract, prebiotics, plant sterols, and stanols) on plasma lipids, lipoproteins, blood pressure, glucose, and insulin levels and their anti-inflammatory and anti-oxidant effects are documented. However, larger, prospective clinical trials are required to confirm such benefits. Such treatments may be recommended when lipid-lowering drugs are neither indicated nor tolerated as well as in order to achieve therapeutic targets and/or overcome residual CV risk.

  16. [Special recommendations for lipid-lowering treatment: efficacy and safety].

    PubMed

    Martinez, Tania Leme da Rocha; Nascimento, Helena Maria do

    2005-10-01

    Pharmacologic lipid-lowering interventions should be monitored periodically to assess efficacy and safety parameters. Statins are usually well-tolerated drugs and major side effects include increased serum liver and muscle enzymes (AST, ALT, CK). Treatment should be stopped or diminished in case of significant increase of AST or ALT (> 3x ULN), or CK (> 10x ULN). Other lipid lowering agents may also produce hepatotoxicity or myositis, especially in association with statins (fibrates and nicotinic acid) or in presence of metabolic abnormalities (thyroid, liver or renal disorders). Nicotinic acid can also increase glucose and uric acid plasma levels. Laboratory tests might be performed prior to hypolipidemic drug treatment and should be repeated every three months during the first year and then at 6-mo intervals. Shorter intervals should be recommended in individual cases.

  17. [Dyslipidemia - when are lipid lowering medications useful in clinical practice?].

    PubMed

    Blum, Manuel R; Stanga, Zeno; Rodondi, Nicolas

    2013-05-08

    Dyslipidemia is one of the main modifiable cardiovascular risk factors. There is strong evidence for the efficacy of lipid-lowering drugs in secondary prevention, as well as in primary prevention for patients at high cardiovascular risk. In primary prevention, indication for lipid-lowering interventions should be based on an individual assessment of the cardiovascular risk and on the LDL cholesterol level, despite less strong evidence for the efficacy of drug-based interventions in low risk patients. Treatment consists of statins, as well as lifestyle modifications such as body weight control and increased physical exercise. The latter constitute the primary intervention in patients at low cardiovascular risk. Secondary dyslipidemias due to an underlying medical condition and familial dyslipidemias such as Familial Hypercholesterolemia and Familial Combined Hyperlipidemia should be identified and treated accordingly, taking into account that the risk scoring systems are not appropriate in these situations.

  18. A Metaanalysis of Interventions to Improve Adherence to Lipid-Lowering Medication

    PubMed Central

    Deichmann, Richard E.; Morledge, Michael D.; Ulep, Robin; Shaffer, Johnathon P.; Davies, Philippa; van Driel, Mieke L.

    2016-01-01

    Background: Inadequate patient adherence to a medication regimen is a major factor in the lack of success in treating hyperlipidemia. Improved adherence rates may result in significantly improved cardiovascular outcomes in populations treated with lipid-lowering therapy. The purpose of this metaanalysis was to evaluate the effectiveness of interventions aimed at improving adherence to lipid-lowering drugs, focusing on measures of adherence and clinical outcomes. Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases through January 14, 2015, and also used the results from previous Cochrane reviews of this title. Randomized controlled trials of adherence-enhancing interventions for lipid-lowering medication in adults in an ambulatory setting with measurable outcomes were evaluated with criteria outlined by the Cochrane Handbook for Systematic Reviews of Interventions. Results: Twenty-seven studies randomly assigning 899,068 participants to a variety of interventions were analyzed. One group of interventions categorized as intensified patient care showed significant improvement in adherence rates when compared to usual care (odds ratio 1.93; 95% confidence interval [CI] 1.29-2.88). Additionally, after <6 months of follow-up, total cholesterol decreased by a mean of 17.15 mg/dL (95% CI 1.17-33.14), while after >6 months total cholesterol decreased by a mean of 17.57 mg/dL (95% CI 14.95-20.19). Conclusion: Healthcare systems that can implement team-based intensified patient care interventions, such as electronic reminders, pharmacist-led interventions, and healthcare professional education of patients, may be successful in improving adherence rates to lipid-lowering medicines. PMID:27660570

  19. Intensive insulin therapy in the medical ICU.

    PubMed

    Van den Berghe, Greet; Wilmer, Alexander; Hermans, Greet; Meersseman, Wouter; Wouters, Pieter J; Milants, Ilse; Van Wijngaerden, Eric; Bobbaers, Herman; Bouillon, Roger

    2006-02-02

    Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units (ICUs), but its role in patients in medical ICUs is unknown. In a prospective, randomized, controlled study of adult patients admitted to our medical ICU, we studied patients who were considered to need intensive care for at least three days. On admission, patients were randomly assigned to strict normalization of blood glucose levels (80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) with the use of insulin infusion or to conventional therapy (insulin administered when the blood glucose level exceeded 215 mg per deciliter [12 mmol per liter], with the infusion tapered when the level fell below 180 mg per deciliter [10 mmol per liter]). There was a history of diabetes in 16.9 percent of the patients. In the intention-to-treat analysis of 1200 patients, intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality (40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group, P=0.33). However, morbidity was significantly reduced by the prevention of newly acquired kidney injury, accelerated weaning from mechanical ventilation, and accelerated discharge from the ICU and the hospital. Although length of stay in the ICU could not be predicted on admission, among 433 patients who stayed in the ICU for less than three days, mortality was greater among those receiving intensive insulin therapy. In contrast, among 767 patients who stayed in the ICU for three or more days, in-hospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent (P=0.009) and morbidity was also reduced. Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU. Although the risk of subsequent death and disease was reduced in patients treated for three or more days, these patients could not be identified

  20. Cardiovascular effects of statins, beyond lipid-lowering properties.

    PubMed

    Mihos, Christos G; Pineda, Andres M; Santana, Orlando

    2014-10-01

    The 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, better known as 'statins', are amongst the most widely used medications in the world. They have become a pivotal component in the primary and secondary prevention of coronary artery and vascular disease. However, a growing amount of evidence has suggested that statins also possess strong pleiotropic effects irrespective of their lipid-lowering properties, which include enhancement of endothelial function, anti-inflammatory and anti-atherothrombotic properties, and immunomodulation. The following provides a comprehensive and updated review of the clinical evidence regarding the pleiotropic effects of statins in cardiovascular disorders and their potential therapeutic benefits.

  1. Neutron Measurements for Intensity Modulated Radiation Therapy

    SciTech Connect

    Ipe, Nisy E.

    2000-04-21

    The beam-on time for intensity modulated radiation therapy (IMRT) is increased significantly compared with conventional radiotherapy treatments. Further, the presence of beam modulation devices may potentially affect neutron production. Therefore, neutron measurements were performed for 15 MV photon beams on a Varian Clinac accelerator to determine the impact of IMRT on neutron dose equivalent to the patient.

  2. Problems of intensive therapy in childhood cancer

    SciTech Connect

    Skelton, J.; Pizzo, P.A.

    1986-07-15

    Tremendous progress has been made in the treatment of childhood cancers. Certain hematologic malignancies have an impressive cure rate with the current intensive antineoplastic treatment regimens. There is optimism that the treatment of children who have advanced stage solid tumors with intensive, multimodality therapy may improve their chances for long-term survival. These treatment programs, though potentially curative, are highly toxic, with severe myelosuppression and damage to other organ systems. An awareness of these potential toxicities, an understanding of how to prevent or minimize certain problems, and the ability to treat those complications which do arise are all essential to the successful management of childhood cancer. 206 references.

  3. D-003 (Saccharum officinarum): The forgotten lipid-lowering agent.

    PubMed

    Awad, Kamal; Penson, Peter; Banach, Maciej

    2016-12-01

    Reduction of elevated cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-C), is essential in primary and secondary prevention of cardiovascular disease (CVD). Therefore there is still a large need for new effective drugs, which would be able to essentially reduce LDL-C and in the consequence CV residual risk. D-003 is a mixture of high aliphatic primary acids purified from sugarcane (Saccharum officinarum) wax. It showed promising hypocholesterolemic effects in both animal and human studies; it significantly lowers both serum total cholesterol (TC) and LDL-C, and increases high-density lipoprotein cholesterol (HDL-C). In addition, it showed a favorable safety profile. In this review, we evaluated the profile of D-003 as a lipid-lowering agent based on data from available preclinical and clinical studies.

  4. Review of clinical studies of fenofibrate in combination with currently approved lipid-lowering drugs.

    PubMed

    Brown, W V

    1989-01-01

    Recent trials have investigated the usefulness of fenofibrate, alone and in combination with other lipid-lowering therapies, in the treatment of hyperlipidemia. Studies of fenofibrate + bile acid sequestrants demonstrate that these two therapies may have an additive effect in reducing total cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol and triglyceride levels in patients with hyperlipoproteinemia or familial hypercholesterolemia. These lipoprotein changes have been associated with a regression of tendon xanthoma. Pharmacokinetic studies have shown that bile acid sequestrants do not alter the absorption or the plasma levels of fenofibrate. The combined use of fenofibrate with bile acid sequestrants has been found to be comparably effective with the new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, synvinolin, with respect to the reduction of total cholesterol and LDL. Although synvinolin was more effective in lowering LDL, VLDL cholesterol and triglycerides were reduced to a greater extent with fenofibrate. Another notable difference was that fenofibrate + bile acids more markedly increased HDL levels. The combination of fenofibrate + nicotinic acid also appears to have a beneficial effect on lipoproteins. These preliminary results indicate that fenofibrate may be a useful addition to the present lipid-lowering drug armamentarium.

  5. More potent lipid lowering effect by rosuvastatin compared to fluvastatin in everolimus treated renal transplant recipients

    PubMed Central

    Robertsen, Ida; Åsberg, Anders; Granseth, Tone; Vethe, Nils Tore; Akhlaghi, Fatemeh; Ghareeb, Mwlod; Molden, Espen; Reier-Nilsen, Morten; Holdaas, Hallvard; Midtvedt, Karsten

    2014-01-01

    Background Dyslipidemia is a risk factor for premature cardiovascular morbidity and mortality in renal transplant recipients (RTR). Pharmacotherapy with mTOR inhibitors aggravates dyslipidemia thus necessitating lipid-lowering therapy with fluvastatin, pravastatin or atorvastatin. These agents may not sufficiently lower lipid levels and therefore a more potent agent like rosuvastatin maybe needed. Methods We have aimed to assess the lipid-lowering effect of rosuvastatin as compared to fluvastatin in RTR receiving everolimus. Safety was assessed as the pharmacokinetic (PK) interaction potential of a rosuvastatin/everolimus combination in RTR. A 12-hour everolimus PK-investigation was performed in twelve stable RTR receiving everolimus and fluvastatin (80 mg/day). Patients were then switched to rosuvastatin (20 mg/day) and a follow-up 12/24-hour PK-investigation of everolimus/rosuvastatin was performed after one month. All other drugs were kept unchanged. Results In RTR already receiving fluvastatin, switching to rosuvastatin further decreased LDL-cholesterol and total cholesterol by 30.2±12.2% (p<0.01) and 18.2±9.6% (p<0.01), respectively. Everolimus AUC0-12 was not affected by concomitant rosuvastatin treatment, 80.3±21.3 μg*h/mL before and 78.5±21.9 μg*h/mL after, respectively (p=0.61). Mean rosuvastatin AUC0-24 was 157±61.7 ng*h/mL, about 3-fold higher than reported in the literature for non-transplants. There were no adverse events and none of the patients had or developed proteinuria. Conclusions Rosuvastatin showed a superior lipid-lowering effect compared to fluvastatin in stable RTR receiving everolimus. The combination of everolimus/rosuvastatin appears to be as safe as the everolimus/fluvastatin combination. PMID:24521776

  6. Virtual micro-intensity modulated radiation therapy.

    PubMed

    Siochi, R A

    2000-11-01

    Virtual micro-intensity modulated radiation therapy (VMIMRT) combines a 10 x 5 mm2 intensity map with a 5 x 10 mm2 intensity map, delivered at orthogonal collimator settings. The superposition of these component maps (CM) yields a 5 x 5 mm2 virtual micro-intensity map (VMIM) that can be delivered with a 1 cm leaf width MLC. A pair of CMs with optimal delivery efficiency and quality must be chosen, since a given VMIM can be delivered using several different pairs. This is possible since, for each group of four VMIM cells that can be covered by an MLC leaf in either collimator orientation, the minimum intensity can be delivered from either collimator setting. By varying the proportions of the minimum values that go into each CM, one can simultaneously minimize the number of potential junction effects and the number of segments required to deliver the VMIM. The minimization is achieved by reducing high leaf direction gradients in the CMs. Several pseudoclinical and random VMIMs were studied to determine the applicability of this new technique. A nine level boost map was also studied to investigate dosimetric and spatial resolution issues. Finally, clinical issues for this technique are discussed.

  7. Rhabdomyolysis: a case study exploring the possible side effect of lipid lowering medication by a HIV positive patient taking a protease inhibitor.

    PubMed

    De Carvalho, Diana; Citro, Mark; Tibbles, Anthony

    2008-12-01

    This case study explores the incidence of rhabdomyolysis in a HIV positive patient that was taking a lipid lowering drug and a protease inhibitor concurrently while under chiropractic treatment for generalized muscular soreness. Dyslipidemia is a very common problem both in the general and HIV population, with many patients being prescribed lipid lowering drugs. While extremely rare, adverse effects of lipid lowering drugs have been documented to include myopathy such as rhabdomyolysis. It is imperative that chiropractors are aware of the possible adverse side effect of lipid lowering drug therapy in their patients complaining of musculoskeletal pain. It is even more important that chiropractors treating the HIV population are aware of the potential interactions between these medications and protease inhibitors to cause myopathy.

  8. Fan-beam intensity modulated proton therapy

    SciTech Connect

    Hill, Patrick; Westerly, David; Mackie, Thomas

    2013-11-15

    Purpose: This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques.Methods: A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0–255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets.Results: Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage

  9. Fan-beam intensity modulated proton therapy

    PubMed Central

    Hill, Patrick; Westerly, David; Mackie, Thomas

    2013-01-01

    Purpose: This paper presents a concept for a proton therapy system capable of delivering intensity modulated proton therapy using a fan beam of protons. This system would allow present and future gantry-based facilities to deliver state-of-the-art proton therapy with the greater normal tissue sparing made possible by intensity modulation techniques. Methods: A method for producing a divergent fan beam of protons using a pair of electromagnetic quadrupoles is described and particle transport through the quadrupole doublet is simulated using a commercially available software package. To manipulate the fan beam of protons, a modulation device is developed. This modulator inserts or retracts acrylic leaves of varying thickness from subsections of the fan beam. Each subsection, or beam channel, creates what effectively becomes a beam spot within the fan area. Each channel is able to provide 0–255 mm of range shift for its associated beam spot, or stop the beam and act as an intensity modulator. Results of particle transport simulations through the quadrupole system are incorporated into the MCNPX Monte Carlo transport code along with a model of the range and intensity modulation device. Several design parameters were investigated and optimized, culminating in the ability to create topotherapy treatment plans using distal-edge tracking on both phantom and patient datasets. Results: Beam transport calculations show that a pair of electromagnetic quadrupoles can be used to create a divergent fan beam of 200 MeV protons over a distance of 2.1 m. The quadrupole lengths were 30 and 48 cm, respectively, with transverse field gradients less than 20 T/m, which is within the range of water-cooled magnets for the quadrupole radii used. MCNPX simulations of topotherapy treatment plans suggest that, when using the distal edge tracking delivery method, many delivery angles are more important than insisting on narrow beam channel widths in order to obtain conformal target coverage

  10. Intensive insulin therapy in septic shock.

    PubMed

    Orford, Neil R

    2006-09-01

    The use of intensive insulin therapy (IIT) to maintain blood glucose level below 8.3 mmol/L is recommended for management of severe sepsis by the Surviving Sepsis guidelines. The recent trials reporting reduced morbidity and mortality in critically ill patients treated with IIT require careful examination, including the subsequent post-hoc analyses. An understanding of the molecular and metabolic mechanisms by which IIT may be beneficial and the evidence that it benefits patients with severe sepsis, and a review of the risks of hypoglycaemia are also necessary when deciding whether to implement IIT in severe sepsis. Patients with severe sepsis are likely to benefit from IIT based on metabolic effects and their prolonged stays in the intensive care unit. The current evidence suggests IIT should be implemented, aiming for the lowest glycaemic range that can be safely achieved while avoiding hypoglycaemia.

  11. Formulation and Evaluation of Nanocrystals of a Lipid Lowering Agent

    PubMed Central

    Louis, Dina

    2016-01-01

    Atorvastatin calcium, the lipid lowering agent, is taken as a model drug characterized by poor water solubility and bioavailability. In this study an attempt was made for preparation of nanocrystals using high pressure homogenization. A number of stabilizers were included as well as polymers at different concentrations, and the formulations were homogenized for ten cycles at a pressure of 1000 bars. The obtained nano crystals were evaluated by determining their size, zeta potential, saturated solubility and dissolution rate. Results revealed that Formulation 3, containing (10: 1) drug to sodium lauryl sulphate ratio, possessed the highest saturated solubility and dissolution rate, and hence was analyzed by X-ray diffraction analysis, differential scanning calorimetry, Fourrier transform infrared spectroscopy and scanning electron microscopy. An in-vivo study was carried out on the successful formulation in comparison to drug powder using rats as experimental animals. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the untreated atorvastatin calcium. PMID:27610148

  12. Formulation and Evaluation of Nanocrystals of a Lipid Lowering Agent.

    PubMed

    Louis, Dina

    2016-01-01

    Atorvastatin calcium, the lipid lowering agent, is taken as a model drug characterized by poor water solubility and bioavailability. In this study an attempt was made for preparation of nanocrystals using high pressure homogenization. A number of stabilizers were included as well as polymers at different concentrations, and the formulations were homogenized for ten cycles at a pressure of 1000 bars. The obtained nano crystals were evaluated by determining their size, zeta potential, saturated solubility and dissolution rate. Results revealed that Formulation 3, containing (10: 1) drug to sodium lauryl sulphate ratio, possessed the highest saturated solubility and dissolution rate, and hence was analyzed by X-ray diffraction analysis, differential scanning calorimetry, Fourrier transform infrared spectroscopy and scanning electron microscopy. An in-vivo study was carried out on the successful formulation in comparison to drug powder using rats as experimental animals. A significant increase in the area under the concentration-time curve Cpmax and MRT for nanocrystals was observed in comparison to the untreated atorvastatin calcium.

  13. Lipid lowering effect of Cinnamomum zeylanicum in hyperlipidaemic albino rabbits.

    PubMed

    Javed, Ijaz; Faisal, Imran; Rahman, Ziaur; Khan, Muhammad Zargham; Muhammad, Faqir; Aslam, Bilal; Ahmad, Mahmood; Shahzadi, Andleeb

    2012-01-01

    The purpose of the present study was to investigate the lipid lowering effect of Cinnamomum zeylanicum (Cinnamon) in hyperlipidaemic albino rabbits. For this purpose, forty eight albino rabbits were randomly divided into eight equal groups; untreated control on normal routine feed, untreated control on butter and cholesterol, treated control on synthetic cholesterol lowering drug simvastatin (Tablet survive (R) 20 mg), three treated groups on three respective doses of C. zeylanicum bark powder and two treated groups on water and methanol extracts of C. zeylanicum bark powder. Butter ad lib and cholesterol powder 500 mg/kg body weight were used to induce experimental hyperlipidaemia in all groups except untreated control group. The results suggested that C. zeylanicum bark powder at the rate of 0.50 g/kg, 0.75 g/kg and methanol extract equivalent to 0.75 g/kg powder produced respective percent reductions in total lipids by 45, 49 and 64; triglycerides by 38, 53 and 60; total cholesterol by 53, 64 and 69 and LDL-cholesterol by 50, 59 and 62. However, at these dosage levels HDL-cholesterol showed respective percent increase of 42, 48 and 53. Nonetheless, C. zeylanicum bark powder at the level of 0.25g/kg and C. zeylanicum extract in water could not significantly reduce lipid profile indicators. Based on these studies, it can safely be said that C. zeylanicum bark powder methanol extract equivalent to 0.75g/kg bark powder and simvastatin (0.6 mg/kg b. wt.) were equieffective in treating hyperlipidaemia.

  14. Combination of simvastatin with berberine improves the lipid-lowering efficacy.

    PubMed

    Kong, Wei-Jia; Wei, Jin; Zuo, Zeng-Yan; Wang, Yue-Ming; Song, Dan-Qing; You, Xue-Fu; Zhao, Li-Xun; Pan, Huai-Ning; Jiang, Jian-Dong

    2008-08-01

    We have identified berberine (BBR) as a novel cholesterol-lowering drug acting through stabilization of the low-density lipoprotein receptor (LDLR) messenger RNA. Because the mechanism differs from that of statins, it is of great interest to examine the lipid-lowering activity of BBR in combination with statins. Our results showed that combination of BBR with simvastatin (SIMVA) increased the LDLR gene expression to a level significantly higher than that in monotherapies. In the treatment of food-induced hyperlipidemic rats, combination of BBR (90 mg/[kg d], oral) with SIMVA (6 mg/[kg d], oral) reduced serum LDL cholesterol by 46.2%, which was more effective than that of the SIMVA (28.3%) or BBR (26.8%) monotherapy (P < .01 for both) and similar to that of SIMVA at 12 mg/(kg d) (43.4%). More effective reduction of serum triglyceride was also achieved with the combination as compared with either monotherapy. Combination of BBR with SIMVA up-regulated the LDLR messenger RNA in rat livers to a level about 1.6-fold higher than the monotherapies did. Significant reduction of liver fat storage and improved liver histology were found after the combination therapy. The therapeutic efficacy of the combination was then evaluated in 63 hypercholesterolemic patients. As compared with monotherapies, the combination showed an improved lipid-lowering effect with 31.8% reduction of serum LDL cholesterol (P < .05 vs BBR alone, P < .01 vs SIMVA alone). Similar efficacies were observed in the reduction of total cholesterol as well as triglyceride in the patients. Our results display the rationale, effectiveness, and safety of the combination therapy for hyperlipidemia using BBR and SIMVA. It could be a new regimen for hypercholesterolemia.

  15. Film Dosimetry for Intensity Modulated Radiation Therapy

    NASA Astrophysics Data System (ADS)

    Benites-Rengifo, J.; Martínez-Dávalos, A.; Celis, M.; Lárraga, J.

    2004-09-01

    Intensity Modulated Radiation Therapy (IMRT) is an oncology treatment technique that employs non-uniform beam intensities to deliver highly conformal radiation to the targets while minimizing doses to normal tissues and critical organs. A key element for a successful clinical implementation of IMRT is establishing a dosimetric verification process that can ensure that delivered doses are consistent with calculated ones for each patient. To this end we are developing a fast quality control procedure, based on film dosimetry techniques, to be applied to the 6 MV Novalis linear accelerator for IMRT of the Instituto Nacional de Neurología y Neurocirugía (INNN) in Mexico City. The procedure includes measurements of individual fluence maps for a limited number of fields and dose distributions in 3D using extended dose-range radiographic film. However, the film response to radiation might depend on depth, energy and field size, and therefore compromise the accuracy of measurements. In this work we present a study of the dependence of Kodak EDR2 film's response on the depth, field size and energy, compared with those of Kodak XV2 film. The first aim is to devise a fast and accurate method to determine the calibration curve of film (optical density vs. doses) commonly called a sensitometric curve. This was accomplished by using three types of irradiation techniques: Step-and-shoot, dynamic and static fields.

  16. [Palliative therapy concepts in intensive care medicine].

    PubMed

    Schuster, M; Ferner, M; Bodenstein, M; Laufenberg-Feldmann, R

    2017-04-01

    Involvement of palliative care is so far not common practice for critically ill patients on surgical intensive care units (ICUs) in Germany. The objectives of palliative care concepts are improvement of patient quality of life by relief of disease-related symptoms using an interdisciplinary approach and support of patients and their relatives considering their current physical, psychological, social and spiritual needs. The need for palliative care can be identified via defined screening criteria. Integration of palliative care can either be realized using a consultative model which focusses on involvement of palliative care consultants or an integrative model which embeds palliative care principles into the routine daily practice by the ICU team. Early integration of palliative care in terms of advance care planning (ACP) can lead to an increase in goals of care discussions and quality of life as well as a decrease of mortality and length of stay on the ICU. Moreover, stress reactions of relatives and ICU staff can be reduced and higher satisfaction with therapy can be achieved. The core of goal of care discussions is professional and well-structured communication between patients, relatives and staff. Consideration of palliative care principles by model-based integration into ICU practice can improve complex intensive care courses of disease in a productive but dignified way without neglecting curative attempts.

  17. Intensity of Therapy Services: What Are the Considerations?

    ERIC Educational Resources Information Center

    Palisano, Robert J.; Murr, Susan

    2009-01-01

    Research on intensity of therapy services is limited and perspectives often vary considerably among families, therapists, administrators, policy makers, and health insurers. In this commentary, the authors share their perspectives on intensity of physical therapy and/or occupational therapy services for children with developmental conditions. Five…

  18. Intensity of Therapy Services: What Are the Considerations?

    ERIC Educational Resources Information Center

    Palisano, Robert J.; Murr, Susan

    2009-01-01

    Research on intensity of therapy services is limited and perspectives often vary considerably among families, therapists, administrators, policy makers, and health insurers. In this commentary, the authors share their perspectives on intensity of physical therapy and/or occupational therapy services for children with developmental conditions. Five…

  19. Improved neurocognitive functions correlate with reduced inflammatory burden in atrial fibrillation patients treated with intensive cholesterol lowering therapy.

    PubMed

    Lappegård, Knut Tore; Pop-Purceleanu, Monica; van Heerde, Waander; Sexton, Joe; Tendolkar, Indira; Pop, Gheorghe

    2013-06-28

    Atrial fibrillation (AF) is associated with increased mortality and morbidity, including risk for cerebral macro- and microinfarctions and cognitive decline, even in the presence of adequate oral anticoagulation. AF is strongly related to increased inflammatory activity whereby anti-inflammatory agents can reduce the risk of new or recurrent AF. However, it is not known whether anti-inflammatory therapy can also modify the deterioration of neurocognitive function in older patients with AF. In the present study, older patients with AF were treated with intensive lipid-lowering therapy with atorvastatin 40 mg and ezetimibe 10 mg, or placebo. We examined the relationship between neurocognitive functions and inflammatory burden. Analysis of inflammatory markers revealed significant reductions in high sensitivity C-reactive protein (hs-CRP), fibroblast growth factor (FGF), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 receptor antagonist (IL-1RA), interleukin (IL)-9, IL-13 and IL-17, and interferon-γ (IFNγ) in the treatment group compared to placebo. Reduction in plasma concentration of IL-1RA, IL-2, IL-9 and IL-12, and macrophage inflammatory protein-1β (MIP-1β) correlated significantly with improvement in the neurocognitive functions memory and speed. Loss of volume in amygdala and hippocampus, as determined by magnetic resonance imaging (MRI), was reduced in the treatment arm, statistically significant for left amygdala. Anti-inflammatory therapy through intensive lipid-lowering treatment with atorvastatin 40 mg and ezetimibe 10 mg can modify the deterioration of neurocognitive function, and the loss of volume in certain cerebral areas in older patients with AF. TRIAL REGISTRATION ClinicalTrials.gov: NCT00449410.

  20. High-Intensity Statin Therapy Is Associated With Improved Survival in Patients With Peripheral Artery Disease.

    PubMed

    Foley, T Raymond; Singh, Gagan D; Kokkinidis, Damianos G; Choy, Ho-Hin K; Pham, Thai; Amsterdam, Ezra A; Rutledge, John C; Waldo, Stephen W; Armstrong, Ehrin J; Laird, John R

    2017-07-15

    The relative benefit of higher statin dosing in patients with peripheral artery disease has not been reported previously. We compared the effectiveness of low- or moderate-intensity (LMI) versus high-intensity (HI) statin dose on clinical outcomes in patients with peripheral artery disease. We reviewed patients with symptomatic peripheral artery disease who underwent peripheral angiography and/or endovascular intervention from 2006 to 2013 who were not taking other lipid-lowering medications. HI statin use was defined as atorvastatin 40-80 mg or rosuvastatin 20-40 mg. Baseline demographics, procedural data, and outcomes were retrospectively analyzed. Among 909 patients, 629 (69%) were prescribed statins, and 124 (13.6%) were treated with HI statin therapy. Mean low-density lipoprotein level was similar in patients on LMI versus HI (80±30 versus 87±44 mg/dL, P=0.14). Demographics including age (68±12 versus 67±10 years, P=0.25), smoking history (76% versus 80%, P=0.42), diabetes mellitus (54% versus 48%, P=0.17), and hypertension (88% versus 89%, P=0.78) were similar between groups (LMI versus HI). There was a higher prevalence of coronary artery disease (56% versus 75%, P=0.0001) among patients on HI statin (versus LMI). After propensity weighting, HI statin therapy was associated with improved survival (hazard ratio for mortality: 0.52; 95% confidence interval, 0.33-0.81; P=0.004) and decreased major adverse cardiovascular events (hazard ratio: 0.58; 95% confidence interval 0.37-0.92, P=0.02). In patients with peripheral artery disease who were referred for peripheral angiography or endovascular intervention, HI statin therapy was associated with improved survival and fewer major adverse cardiovascular events compared with LMI statin therapy. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  1. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA): a randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase.

    PubMed

    Gupta, Ajay; Thompson, David; Whitehouse, Andrew; Collier, Tim; Dahlof, Bjorn; Poulter, Neil; Collins, Rory; Sever, Peter

    2017-06-24

    In blinded randomised controlled trials, statin therapy has been associated with few adverse events (AEs). By contrast, in observational studies, larger increases in many different AEs have been reported than in blinded trials. In the Lipid-Lowering Arm of the Anglo-Scandinavian Cardiac Outcomes Trial, patients aged 40-79 years with hypertension, at least three other cardiovascular risk factors, and fasting total cholesterol concentrations of 6·5 mmol/L or lower, and who were not taking a statin or fibrate, had no history of myocardial infarction, and were not being treated for angina were randomly assigned to atorvastatin 10 mg daily or matching placebo in a randomised double-blind placebo-controlled phase. In a subsequent non-randomised non-blind extension phase (initiated because of early termination of the trial because efficacy of atorvastatin was shown), all patients were offered atorvastatin 10 mg daily open label. We classified AEs using the Medical Dictionary for Regulatory Activities. We blindly adjudicated all reports of four prespecified AEs of interest-muscle-related, erectile dysfunction, sleep disturbance, and cognitive impairment-and analysed all remaining AEs grouped by system organ class. Rates of AEs are given as percentages per annum. The blinded randomised phase was done between February, 1998, and December, 2002; we included 101 80 patients in this analysis (5101 [50%] in the atorvastatin group and 5079 [50%] in the placebo group), with a median follow-up of 3·3 years (IQR 2·7-3·7). The non-blinded non-randomised phase was done between December, 2002, and June, 2005; we included 9899 patients in this analysis (6409 [65%] atorvastatin users and 3490 [35%] non-users), with a median follow-up of 2·3 years (2·2-2·4). During the blinded phase, muscle-related AEs (298 [2·03% per annum] vs 283 [2·00% per annum]; hazard ratio 1·03 [95% CI 0·88-1·21]; p=0·72) and erectile dysfunction (272 [1·86% per annum] vs 302 [2·14% per annum]; 0

  2. Low intensity laser therapy: the clinical approach

    NASA Astrophysics Data System (ADS)

    Kahn, Fred

    2006-02-01

    Recently, there has been significant improvement in the process of research and application of Low Intensity Laser Therapy (LILT). Despite this positive direction, a wide discrepancy between the research component and clinical understanding of the technology remains. In our efforts to achieve better clinical results and more fully comprehend the mechanisms of interaction between light and cells, further studies are required. The clinical results presented in this paper are extrapolated from a wide range of musculoskeletal problems including degenerative osteoarthritis, repetitive motion injuries, sports injuries, etc. The paper includes three separate clinical studies comprising 151, 286 and 576 consecutive patient discharges at our clinic. Each patient studied received a specific course of treatment that was designed for that individual and was modified on a continuing basis as the healing process advanced. On each visit, clinical status correlation with the duration, dosage and other parameters was carried out. The essentials of the treatment consisted of a three stage approach. This involved a photon stream emanating from a number of specified gallium-aluminum-arsenide diodes; stage one, red light array, stage two consisting of an array of infrared diodes and stage three consisting of the application of an infrared laser diode probe. On average, each of these groups required less than 10 treatments per patient and resulted in a significant improvement / cure rate greater than 90% in all conditions treated. This report clearly demonstrates the benefits of LILT, indicating that it should be more widely adapted in all medical therapeutic settings.

  3. Robust optimization of intensity modulated proton therapy

    SciTech Connect

    Liu Wei; Zhang Xiaodong; Li Yupeng; Mohan, Radhe

    2012-02-15

    Purpose: Intensity modulated proton therapy (IMPT) is highly sensitive to range uncertainties and uncertainties caused by setup variation. The conventional inverse treatment planning of IMPT optimized based on the planning target volume (PTV) is not often sufficient to ensure robustness of treatment plans. In this paper, a method that takes the uncertainties into account during plan optimization is used to mitigate the influence of uncertainties in IMPT. Methods: The authors use the so-called ''worst-case robust optimization'' to render IMPT plans robust in the face of uncertainties. For each iteration, nine different dose distributions are computed--one each for {+-} setup uncertainties along anteroposterior (A-P), lateral (R-L) and superior-inferior (S-I) directions, for {+-} range uncertainty, and the nominal dose distribution. The worst-case dose distribution is obtained by assigning the lowest dose among the nine doses to each voxel in the clinical target volume (CTV) and the highest dose to each voxel outside the CTV. Conceptually, the use of worst-case dose distribution is similar to the dose distribution achieved based on the use of PTV in traditional planning. The objective function value for a given iteration is computed using this worst-case dose distribution. The objective function used has been extended to further constrain the target dose inhomogeneity. Results: The worst-case robust optimization method is applied to a lung case, a skull base case, and a prostate case. Compared with IMPT plans optimized using conventional methods based on the PTV, our method yields plans that are considerably less sensitive to range and setup uncertainties. An interesting finding of the work presented here is that, in addition to reducing sensitivity to uncertainties, robust optimization also leads to improved optimality of treatment plans compared to the PTV-based optimization. This is reflected in reduction in plan scores and in the lower normal tissue doses for the

  4. Intensive diabetes therapy and ocular surgery in type 1 diabetes.

    PubMed

    Aiello, Lloyd Paul; Sun, Wanjie; Das, Arup; Gangaputra, Sapna; Kiss, Szilard; Klein, Ronald; Cleary, Patricia A; Lachin, John M; Nathan, David M

    2015-04-30

    The Diabetes Control and Complications Trial (DCCT) showed a beneficial effect of 6.5 years of intensive glycemic control on retinopathy in patients with type 1 diabetes. Between 1983 and 1989, a total of 1441 patients with type 1 diabetes in the DCCT were randomly assigned to receive either intensive diabetes therapy or conventional therapy aimed at preventing hyperglycemic symptoms. They were treated and followed until 1993. Subsequently, 1375 of these patients were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. The self-reported history of ocular surgical procedures was obtained annually. We evaluated the effect of intensive therapy as compared with conventional therapy on the incidence and cost of ocular surgery during these two studies. Over a median follow-up of 23 years, 130 ocular operations were performed in 63 of 711 patients assigned to intensive therapy (8.9%) and 189 ocular operations in 98 of 730 patients assigned to conventional therapy (13.4%) (P<0.001). After adjustment for DCCT baseline factors, intensive therapy was associated with a reduction in the risk of any diabetes-related ocular surgery by 48% (95% confidence interval [CI], 29 to 63; P<0.001) and a reduction in the risk of all such ocular procedures by 37% (95% CI, 12 to 55; P=0.01). Forty-two patients who received intensive therapy and 61 who received conventional therapy underwent cataract extraction (adjusted risk reduction with intensive therapy, 48%; 95% CI, 23 to 65; P=0.002); 29 patients who received intensive therapy and 50 who received conventional therapy underwent vitrectomy, retinal-detachment surgery, or both (adjusted risk reduction, 45%; 95% CI, 12 to 66; P=0.01). The costs of surgery were 32% lower in the intensive-therapy group. The beneficial effects of intensive therapy were fully attenuated after adjustment for mean glycated hemoglobin levels over the entire follow-up. Intensive therapy in patients with type 1

  5. Long-term Effectiveness of Intensive Therapy in Chronic Stroke.

    PubMed

    Wu, Xiaotian; Guarino, Peter; Lo, Albert C; Peduzzi, Peter; Wininger, Michael

    2016-07-01

    Background While recent clinical trials involving robot-assisted therapy have failed to show clinically significant improvement versus conventional therapy, it is possible that a broader strategy of intensive therapy-to include robot-assisted rehabilitation-may yield clinically meaningful outcomes. Objective To test the immediate and sustained effects of intensive therapy (robot-assisted therapy plus intensive conventional therapy) on outcomes in a chronic stroke population. Methods A multivariate mixed-effects model adjusted for important covariates was established to measure the effect of intensive therapy versus usual care. A total of 127 chronic stroke patients from 4 Veterans Affairs medical centers were randomized to either robot-assisted therapy (n = 49), intensive comparison therapy (n = 50), or usual care (n = 28), in the VA-ROBOTICS randomized clinical trial. Patients were at least 6 months poststroke, of moderate-to-severe upper limb impairment. The primary outcome measure was the Fugl-Meyer Assessment at 12 and 36 weeks. Results There was significant benefit of intensive therapy over usual care on the Fugl-Meyer Assessment at 12 weeks with a mean difference of 4.0 points (95% CI = 1.3-6.7); P = .005; however, by 36 weeks, the benefit was attenuated (mean difference 3.4; 95% CI = -0.02 to 6.9; P = .05). Subgroup analyses showed significant interactions between treatment and age, treatment and time since stroke. Conclusions Motor benefits from intensive therapy compared with usual care were observed at 12 and 36 weeks posttherapy; however, this difference was attenuated at 36 weeks. Subgroups analysis showed that younger age, and a shorter time since stroke were associated with greater immediate and long-term improvement of motor function. © The Author(s) 2015.

  6. The lipid lowering effect of plant sterol ester capsules in hypercholesterolemic subjects

    PubMed Central

    Acuff, Robert V; Cai, David J; Dong, Zhi-Ping; Bell, Doris

    2007-01-01

    Background Foods enriched with phytosterols have been proven to be an effective therapy to improve blood lipid profiles. However, none of the studies have investigated the efficacy in lipid lowering of plant sterol esters (PSE) in capsule form. The objective of this study is to determine if the plant sterol esters (PSE) in capsule form (1.3 grams of PSE/day) lowered plasma cholesterol levels and lipid ratios in free-living hypercholesterolemic subjects during a 4-week intervention period. Methods Sixteen subjects participated in a double-blind, placebo-controlled, sequential study with a 4-week placebo phase followed by a 2-week wash-out period and a 4-week treatment phase. Subjects were instructed to maintain stable diet pattern and physical activities. Blood samples were collected at 7, 21 and 28 days of each phase. The primary measurements were change in plasma total cholesterol (TC), HDL-cholesterol (HDL) and LDL-cholesterol (LDL) between phases and within each phase. The secondary measurements were change in triglycerides, lipoprotein ratios (TC/HDL, LDL/HDL) and C-reactive protein (CRP). Results In comparison to placebo, LDL-cholesterol was significantly reduced by 7% and 4% (P < 0.05) at both week 3 and week 4; HDL at week 3 of the treatment was significantly increased by 9% (P < 0.01), but not at week 4 (4%); total cholesterol was not significantly different from placebo throughout the period, TC/HDL and LDL/HDL were significantly reduced by (8%, 8%, 6%, 10%, respectively) (P < 0.01) at both week 3 and week 4. CRP and triglycerides did not differ either between the two phases or during the treatment phase. Conclusion In conclusion, plant sterol ester capsule is effective in improving lipid profiles among hypercholesterolemic subjects in a free-living setting at the minimum dosage recommended by FDA. The significant improved lipid profiles were reached after three weeks of administration. To achieve better lipid lowering results, higher dosages and

  7. Occupational Therapy in the Intensive Care Unit: A Systematic Review.

    PubMed

    Weinreich, Mark; Herman, Jennifer; Dickason, Stephanie; Mayo, Helen

    2017-07-01

    This paper is a synthesis of the available literature on occupational therapy interventions performed in the adult intensive care unit (ICU). The databases of Ovid MEDLINE, Embase, the Cochrane Library, ClinicalTrials.gov and CINAHL databases were systematically searched from inception through August 2016 for studies of adults who received occupational therapy interventions in the ICU. Of 1,938 citations reviewed, 10 studies met inclusion criteria. Only one study explicitly discussed occupational therapy interventions performed and only one study specifically tested the efficacy of occupational therapy. Future research is needed to clarify the specific interventions and role of occupational therapy in the ICU and the efficacy of these interventions.

  8. Physical Therapy Intervention in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Garber, June

    2013-01-01

    This article presents the elements of the Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence-based and the suggested timing of these interventions is primarily based on practice knowledge from expert…

  9. [Intensive therapy for patients with Guillian-Barré syndrome].

    PubMed

    Buus, Lone; Tønnesen, Else K

    2014-10-13

    Guillain-Barré syndrome is the leading cause of acute flaccid paralysis in the industrialized world. Approximately 25% of the patients suffering from Guillain-Barré syndrome develop respiratory failure requiring mechanical ventilation and intensive therapy. We seek answers to when it is optimal to start respiratory supportive therapy and review various complications associated with Guillain-Barré syndrome.

  10. Physical Therapy Intervention in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Garber, June

    2013-01-01

    This article presents the elements of the Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence-based and the suggested timing of these interventions is primarily based on practice knowledge from expert…

  11. Intense Pulsed Light Therapy for Skin Rejuvenation.

    PubMed

    DiBernardo, Barry E; Pozner, Jason N

    2016-07-01

    Intense pulsed light (IPL), also known as pulsed light and broad band light, is a nonlaser light source used to treat a variety of vascular and pigmented lesions, photo damage, active acne, and unwanted hair. Current IPL systems are much improved from older-generation devices with better calibration, integrated cooling, and improved tuning. These devices are extremely popular because of their versatility and are often the first devices recommended and purchased in many offices. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Insulin therapy in the pediatric intensive care unit

    USDA-ARS?s Scientific Manuscript database

    Hyperglycemia is a major risk factor for increased morbidity and mortality in the intensive care unit. Insulin therapy has emerged in adult intensive care units, and several pediatric studies are currently being conducted. This review discusses hyperglycemia and the effects of insulin on metabolic a...

  13. Stuttering: An Account of Intensive Demonstration Therapy. Publication N. 8.

    ERIC Educational Resources Information Center

    Starkweather, C. Woodruff

    Presented is a summary of a 5 week program of intensive demonstration therapy conducted with three adult severe stutterers by three master clinicians aided by seven consultants and 15 participating fellows. A main purpose of the institute is said to have been the improvement of student clinicians through demonstration of intensive therapy…

  14. Therapy: Intensive glucose control in the ICU: is sugar nice?

    PubMed

    Sacks, David B

    2009-09-01

    intensive insulin therapy is extensively used to lower blood glucose concentrations in critically ill patients hospitalized within the intensive care unit. The discovery by the nice-SUgAr study investigators that tight glucose control in this setting might actually increase mortality has generated considerable discussion about the wisdom of this approach.

  15. Intensive Insulin Therapy in Severely Burned Pediatric Patients

    PubMed Central

    Jeschke, Marc G.; Kulp, Gabriela A.; Kraft, Robert; Finnerty, Celeste C.; Mlcak, Ron; Lee, Jong O.; Herndon, David N.

    2010-01-01

    Rationale: Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality. Objectives: To determine whether intensive insulin therapy is associated with improved post-burn morbidity. Methods: A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n = 60) or control (n = 179). Measurements and Main Results: Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acute-phase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P < 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P < 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P < 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P < 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P = 0.14). Conclusions: In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309). PMID:20395554

  16. Intensive insulin therapy and pentastarch resuscitation in severe sepsis.

    PubMed

    Brunkhorst, Frank M; Engel, Christoph; Bloos, Frank; Meier-Hellmann, Andreas; Ragaller, Max; Weiler, Norbert; Moerer, Onnen; Gruendling, Matthias; Oppert, Michael; Grond, Stefan; Olthoff, Derk; Jaschinski, Ulrich; John, Stefan; Rossaint, Rolf; Welte, Tobias; Schaefer, Martin; Kern, Peter; Kuhnt, Evelyn; Kiehntopf, Michael; Hartog, Christiane; Natanson, Charles; Loeffler, Markus; Reinhart, Konrad

    2008-01-10

    The role of intensive insulin therapy in patients with severe sepsis is uncertain. Fluid resuscitation improves survival among patients with septic shock, but evidence is lacking to support the choice of either crystalloids or colloids. In a multicenter, two-by-two factorial trial, we randomly assigned patients with severe sepsis to receive either intensive insulin therapy to maintain euglycemia or conventional insulin therapy and either 10% pentastarch, a low-molecular-weight hydroxyethyl starch (HES 200/0.5), or modified Ringer's lactate for fluid resuscitation. The rate of death at 28 days and the mean score for organ failure were coprimary end points. The trial was stopped early for safety reasons. Among 537 patients who could be evaluated, the mean morning blood glucose level was lower in the intensive-therapy group (112 mg per deciliter [6.2 mmol per liter]) than in the conventional-therapy group (151 mg per deciliter [8.4 mmol per liter], P<0.001). However, at 28 days, there was no significant difference between the two groups in the rate of death or the mean score for organ failure. The rate of severe hypoglycemia (glucose level, < or = 40 mg per deciliter [2.2 mmol per liter]) was higher in the intensive-therapy group than in the conventional-therapy group (17.0% vs. 4.1%, P<0.001), as was the rate of serious adverse events (10.9% vs. 5.2%, P=0.01). HES therapy was associated with higher rates of acute renal failure and renal-replacement therapy than was Ringer's lactate. The use of intensive insulin therapy placed critically ill patients with sepsis at increased risk for serious adverse events related to hypoglycemia. As used in this study, HES was harmful, and its toxicity increased with accumulating doses. (ClinicalTrials.gov number, NCT00135473.) 2008 Massachusetts Medical Society

  17. A REVIEW OF LOW-INTENSITY ULTRASOUND FOR CANCER THERAPY

    PubMed Central

    WOOD, ANDREW K. W.; SEHGAL, CHANDRA M.

    2015-01-01

    The literature describing the use of low-intensity ultrasound in four major areas of cancer therapy was reviewed - sonodynamic therapy, ultrasound mediated chemotherapy, ultrasound mediated gene delivery and antivascular ultrasound therapy. Each technique consistently resulted in the death of cancer cells and the bioeffects of ultrasound were primarily attributed to thermal actions and inertial cavitation. In each therapeutic modality, theranostic contrast agents composed of microbubbles played a role in both therapy and vascular imaging. The development of these agents is important as it establishes a therapeutic-diagnostic platform which can monitor the success of anti-cancer therapy. Little attention, however, has been given to either the direct assessment of the underlying mechanisms of the observed bioeffects or to the viability of these therapies in naturally occurring cancers in larger mammals; if such investigations provided encouraging data there could be a prompt application of a therapy technique in treating cancer patients. PMID:25728459

  18. Plasma Coenzyme Q10 Predicts Lipid-lowering Response to High-Dose Atorvastatin

    PubMed Central

    Pacanowski, Michael A.; Frye, Reginald F.; Enogieru, Osatohanmen; Schofield, Richard S.; Zineh, Issam

    2008-01-01

    Background Coenzyme Q10 (CoQ10) is a provitamin synthesized via the HMG-CoA reductase pathway, and thus may serve as a potential marker of intrinsic HMG-CoA reductase activity. HMG-CoA reductase inhibitors (statins) decrease CoQ10, although it is unclear whether this is due to reductions in lipoproteins, which transport CoQ10. Objectives We evaluated whether baseline plasma CoQ10 concentrations predict the lipid-lowering response to high-dose atorvastatin, and to what extent CoQ10 changes following atorvastatin therapy depend on lipoprotein changes. Methods Individuals without dyslipidemia or known cardiovascular disease (n=84) received atorvastatin 80 mg daily for 16 weeks. Blood samples collected at baseline and after 4, 8, and 16 weeks of treatment were assayed for CoQ10. Results Individuals with higher baseline CoQ10:LDL-C ratios displayed diminished absolute and percent LDL-C reductions at 8 and 16 weeks of atorvastatin treatment (P<0.001 to 0.01). After 16 weeks of atorvastatin, plasma CoQ10 decreased 45% from 762±301 ng/ml to 374±150 ng/ml (P<0.001). CoQ10 changes were correlated with LDL-C and apolipoprotein B changes (r=0.27-0.38, P=0.001-0.02), but remained significant when normalized to all lipoproteins. CoQ10 changes were not associated with adverse drug reactions. Conclusion Baseline CoQ10:LDL-C ratio was associated with the degree of LDL-C response to atorvastatin. Atorvastatin decreased CoQ10 concentrations in a manner that was not completely dependent on lipoprotein changes. The utility of CoQ10 as a predictor of atorvastatin response should be further explored in patients with dyslipidemia. PMID:19649137

  19. Current cardiovascular risk management patterns with special focus on lipid lowering in daily practice in Switzerland.

    PubMed

    Jaussi, Andres; Noll, Georg; Meier, Bernhard; Darioli, Roger

    2010-06-01

    There may be a considerable gap between LDL cholesterol (LDL-C) and blood pressure (BP) goal values recommended by the guidelines and results achieved in daily practice. Prospective cross-sectional survey of cardiovascular disease risk profiles and management with focus on lipid lowering and BP lowering in clinical practice. In phase 1, the cardiovascular risk of patients with known lipid profile visiting their general practitioner was anonymously assessed in accordance to the PROCAM-score. In phase 2, high-risk patients who did not achieve LDL-C goal less than 2.6 mmol/l in phase 1 could be further documented. Six hundred thirty-five general practitioners collected the data of 23 892 patients with known lipid profile. Forty percent were high-risk patients (diabetes mellitus or coronary heart disease or PROCAM-score >20%), compared with 27% estimated by the physicians. Goal attainment rate was almost double for BP than for LDL-C in high-risk patients (62 vs. 37%). Both goals were attained by 25%. LDL-C values in phase 1 and 2 were available for 3097 high-risk patients not at LDL-C goal in phase 1; 32% of patients achieved LDL-C goal of less than 2.6 mmol/l after a mean of 17 weeks. The most successful strategies for LDL-C reduction were implemented in only 22% of the high-risk patients. Although patients at high cardiovascular risk were treated more intensively than low or medium risk patients, the majority remained insufficiently controlled, which is an incentive for intensified medical education. Adequate implementation of Swiss and International guidelines would expectedly contribute to improved achievement of LDL-C and BP goal values in daily practice.

  20. Physical therapy intervention in the neonatal intensive care unit.

    PubMed

    Byrne, Eilish; Garber, June

    2013-02-01

    This article presents the elements of the Intervention section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy interventions presented in this path are evidence-based and the suggested timing of these interventions is primarily based on practice knowledge from expert therapists, with supporting evidence cited. Physical therapy intervention in the NICU is infant-driven and focuses on providing family-centered care. In this context, interventions to facilitate a calm behavioral state and motor organization in the infant, address positioning and handling of the infant, and provide movement therapy are presented.

  1. Intensive Cognitive Therapy for PTSD: A Feasibility Study

    PubMed Central

    Ehlers, Anke; Clark, David M.; Hackmann, Ann; Grey, Nick; Liness, Sheena; Wild, Jennifer; Manley, John; Waddington, Louise; McManus, Freda

    2010-01-01

    Background: Cognitive Behaviour Therapy (CBT) of anxiety disorders is usually delivered in weekly or biweekly sessions. There is evidence that intensive CBT can be effective in phobias and obsessive compulsive disorder. Studies of intensive CBT for posttraumatic stress disorder (PTSD) are lacking. Method: A feasibility study tested the acceptability and efficacy of an intensive version of Cognitive Therapy for PTSD (CT-PTSD) in 14 patients drawn from consecutive referrals. Patients received up to 18 hours of therapy over a period of 5 to 7 working days, followed by 1 session a week later and up to 3 follow-up sessions. Results: Intensive CT-PTSD was well tolerated and 85.7 % of patients no longer had PTSD at the end of treatment. Patients treated with intensive CT-PTSD achieved similar overall outcomes as a comparable group of patients treated with weekly CT-PTSD in an earlier study, but the intensive treatment improved PTSD symptoms over a shorter period of time and led to greater reductions in depression. Conclusions: The results suggest that intensive CT-PTSD is a feasible and promising alternative to weekly treatment that warrants further evaluation in randomized trials. PMID:20573292

  2. A US Claims-Based Analysis of Real-World Lipid-Lowering Treatment Patterns in Patients With High Cardiovascular Disease Risk or a Previous Coronary Event.

    PubMed

    Quek, Ruben G W; Fox, Kathleen M; Wang, Li; Li, Lu; Gandra, Shravanthi R; Wong, Nathan D

    2016-02-15

    The objective was to examine real-world treatment patterns of lipid-lowering therapies and their possible associated intolerance and/or ineffectiveness in patients with high cardiovascular disease (CVD) risk initiating statins and/or ezetimibe. Patients aged ≥18 years who initiated statins and/or ezetimibe from January 01, 2007, to June 30, 2011, were retrospectively identified from the IMS LifeLink PharMetrics Plus commercial claims database. Patients were further classified into 2 cohorts: (1) history of cardiovascular event (CVE) and (2) history of coronary heart disease risk equivalent (CHD RE). Patients had continuous health plan enrollment ≥1 year pre- and post-index date (statin and/or ezetimibe initiation date). Primary outcomes were index statin intensity, treatment modifications, possible associated statin/nonstatin intolerance and/or ineffectiveness issues (based on treatment modification), and time-to-treatment modifications. Analyses for each cohort were stratified by age group (<65 and ≥65 years). A total of 41,934 (history of CVE) and 170,344 patients (history of CHD RE) were included. On the index date, 8.8% to 25.1% of patients were initiated on high-intensity statin. Among patients aged <65, 79.2% and 48.8% of those with history of CVE and 78.6% and 47.3% of those with a history of CHD RE had ≥1 and 2 treatment modifications, respectively. Among all patients, 24.6% to 25.6% had possible statin intolerance and/or ineffectiveness issues after accounting for second treatment modification (if any). In conclusion, in patients with high CVD risk, index statin treatment modifications that imply possible statin intolerance and/or ineffectiveness were frequent; low use of high-intensity statins indicates unmet need in the management of hyperlipidemia and possible remaining unaccounted CVD residual risk. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  3. [Lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system].

    PubMed

    Chen, Kan; Wang, Chang-Qian; Fan, Yu-Qi; Han, Zhi-Hua; Wang, Yue; Gao, Lin; Zeng, Hua-Su

    2017-02-25

    The present study aimed to study lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system. Zebrafish were fed with high fat diet to establish a hyperlipemia model, then fasted and bathed with seven traditional Chinese medicine monomers stigmasterol, triacontanol, chrysophanol, vanillic acid, shikimic acid, polydatin and oleanolic acid respectively. The oil red O staining was used to detect the blood lipids of zebrafish. Serum total cholesterol and triglyceride levels were detected to validate the lipid-lowering effect. The result showed that a zebrafish model of hyperlipemia could be established by feeding larvae zebrafish with high fat diet. Among the seven traditional Chinese medicine monomers, chrysophanol had lipid-lowering effect. Chrysophanol significantly reduced serum total cholesterol and triglyceride levels in adult zebrafish fed with high fat diet. Chrysophanol accelerated peristalsis frequency of zebrafish intestine and the excretion of high fat food. It is concluded that chrysophanol has lipid- lowering effect in zebrafish, and the mechanism of the effect may be due to the roles of chrysophanol in reducing lipid absorption from gastrointestinal tract and accelerating the excretion of food.

  4. The lipid lowering drug lovastatin protects against doxorubicin-induced hepatotoxicity

    SciTech Connect

    Henninger, Christian; Huelsenbeck, Johannes; Huelsenbeck, Stefanie; Grösch, Sabine; Lackner, Karl J.; Kaina, Bernd; Fritz, Gerhard

    2012-05-15

    Liver is the main detoxifying organ and therefore the target of high concentrations of genotoxic compounds, such as environmental carcinogens and anticancer drugs. Here, we investigated the usefulness of lovastatin, which is nowadays widely used for lipid lowering purpose, as a hepatoprotective drug following the administration of the anthracycline derivative doxorubicin in vivo. To this end, BALB/c mice were exposed to either a single high dose or three consecutive low doses of doxorubicin. Acute and subacute hepatotoxicities were analyzed with or without lovastatin co-treatment. Lovastatin protected the liver against doxorubicin-induced acute pro-inflammatory and pro-fibrotic stress responses as indicated by an attenuated mRNA expression of tumor necrosis factor alpha (TNFα) and connective tissue growth factor (CTGF), respectively. Hepatoprotection by lovastatin was due to a reduced induction of DNA damage following doxorubicin treatment. The statin also mitigated subacute anthracycline-provoked hepatotoxicity as shown on the level of doxorubicin- and epirubicin-stimulated CTGF mRNA expression as well as histopathologically detectable fibrosis and serum concentration of marker enzymes of hepatotoxicity (GPT/GLDH). Kidney damage following doxorubicin exposure was not detectable under our experimental conditions. Moreover, lovastatin showed multiple inhibitory effects on doxorubicin-triggered hepatic expression of genes involved in oxidative stress response, drug transport, DNA repair, cell cycle progression and cell death. Doxorubicin also stimulated the formation of ceramides. Ceramide production, however, was not blocked by lovastatin, indicating that hepatoprotection by lovastatin is independent of the sphingolipid metabolism. Overall, the data show that lovastatin is hepatoprotective following genotoxic stress induced by anthracyclines. Based on the data, we hypothesize that statins might be suitable to lower hepatic injury following anthracycline

  5. Effects of Intensive versus Non-Intensive Physical Therapy on Children with Cerebral Palsy.

    PubMed

    Rahman, M A; Zaman, M M; Rahman, M M; Moniruzzaman, M; Ahmed, B; Chhobi, F K; Rahman, N; Akter, M R

    2016-07-01

    Cerebral Palsy (CP) is one of the most common causes of all childhood disorders. There are tone, posture and movements difficulty due to non-progressive damage to the immature brain in CP. The hallmark of CP is a disability in the development of gross motor function (GMF). The influence of gross motor development on fine motor development is more important in early developmental period, specially under three years old and in children with CP. Various therapeutic interventions have been used in the management of GMF development. Among them physical therapy is the most common intervention in CP and is usually a component of mandated programs. Physical therapy means physical stimulations in the form of various therapeutic exercises, touch, massage, limbs and trunk movement, balancing and coordination training, gait and ambulation training, cognitive stimulation as well as speech, language and occupational therapy. Our study focused to see the effect by short term intensive versus non-intensive physical therapy on children GMF development by using gross motor function measure (GMFM) Score sheet, GMFM-88, version 1.0. Study provides the information that physical therapy intervention is effective in GMF development and intensive interventions are more effective in children with spastic CP than non-intensive one. Study also inform that the more early treatment the more effective result.

  6. Clinical implementation of intensity-modulated arc therapy.

    PubMed

    Shepard, David M; Cao, Daliang

    2011-01-01

    Intensity-modulated arc therapy (IMAT) is a rotational approach to radiation therapy delivered on a conventional linear accelerator using a conventional multileaf collimator. There are 2 key advantages of IMAT. First, the rotational nature of the delivery provides great flexibility in shaping each dose distribution. As a result, IMAT can provide dosimetric advantages relative to fixed-field intensity-modulated radiation therapy (IMRT). The second advantage is the highly efficient nature of the delivery. For centers with an active IMRT program, the clinical implementation of IMAT should be relatively straightforward. For clinical implementation of IMAT, it is important to fully characterize the accuracy of the dose model used, and the performance of the quality assurance equipment.

  7. High Intensity Focused Ultrasound Tumor Therapy System and Its Application

    NASA Astrophysics Data System (ADS)

    Sun, Fucheng; He, Ye; Li, Rui

    2007-05-01

    At the end of last century, a High Intensity Focused Ultrasound (HIFU) tumor therapy system was successfully developed and manufactured in China, which has been already applied to clinical therapy. This article aims to discuss the HIFU therapy system and its application. Detailed research includes the following: power amplifiers for high-power ultrasound, ultrasound transducers with large apertures, accurate 3-D mechanical drives, a software control system (both high-voltage control and low-voltage control), and the B-mode ultrasonic diagnostic equipment used for treatment monitoring. Research on the dosage of ultrasound required for tumour therapy in multiple human cases has made it possible to relate a dosage formula, presented in this paper, to other significant parameters such as the volume of thermal tumor solidification, the acoustic intensity (I), and the ultrasound emission time (tn). Moreover, the HIFU therapy system can be applied to the clinical treatment of both benign and malignant tumors in the pelvic and abdominal cavity, such as uterine fibroids, liver cancer and pancreatic carcinoma.

  8. Optimizing antibiotic therapy in the intensive care unit setting

    PubMed Central

    Kollef, Marin H

    2001-01-01

    Antibiotics are one of the most common therapies administered in the intensive care unit setting. In addition to treating infections, antibiotic use contributes to the emergence of resistance among pathogenic microorganisms. Therefore, avoiding unnecessary antibiotic use and optimizing the administration of antimicrobial agents will help to improve patient outcomes while minimizing further pressures for resistance. This review will present several strategies aimed at achieving optimal use of antimicrobial agents. It is important to note that each intensive care unit should have a program in place which monitors antibiotic utilization and its effectiveness. Only in this way can the impact of interventions aimed at improving antibiotic use (e.g. antibiotic rotation, de-escalation therapy) be evaluated at the local level. PMID:11511331

  9. Pravastatin and cardiovascular outcomes stratified by baseline eGFR in the lipid- lowering component of ALLHAT.

    PubMed

    Rahman, Mahboob; Baimbridge, Charles; Davis, Barry R; Barzilay, Joshua I; Basile, Jan N; Henriquez, Mario A; Huml, Anne; Kopyt, Nelson; Louis, Gail T; Pressel, Sara L; Rosendorff, Clive; Sastrasinh, Sithiporn; Stanford, Carol

    2013-10-01

    The role of statins in preventing cardiovascular outcomes in patients with chronic kidney disease (CKD) is unclear. This paper compares cardiovascular outcomes with pravastatin vs. usual care, stratified by baseline estimated glomerular filtration rate (eGFR). Post-hoc analyses of a prospective randomized open-label clinical trial; 10,151 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) were randomized to pravastatin 40 mg/day or usual care. Mean follow-up was 4.8 years. Through Year 6, total cholesterol declined in pravastatin (-20.7%) and usualcare groups (-11.2%). Use of statin therapy in the pravastatin group was 89.8% (Year 2) and 87.0% (Year 6). Usual-care group statin use increased from 8.2% (Year 2) to 23.5% (Year 6). By primary intention-to-treat analyses, no significant differences were seen between groups for coronary heart disease (CHD), total mortality or combined cardiovascular disease; findings were consistent across eGFR strata. In exploratory "as-treated" analyses (patients actually using pravastatin vs. not using), pravastatin therapy was associated with lower mortality (HR = 0.76 (0.68 - 0.85), p<0.001) and lover CHD (HR=0.84 (0.73-0.97), p=0.01), but not combined cardiovascular disease (HR=0.95 (0.88-1.04), p=0.30). Total cholesterol reduction of 10 mg/dl from baseline to Year 2 was associated with 5% lower CHD risk. In hypertensive patients with moderate dyslipidemia, pravastatin was not superior to usual care in preventing total mortality or CHD independent of baseline eGFR level. However, exploratory "as-treated" analyses suggest improved mortality and CHD risk in participants using pravastatin, and decreased CHD events associated with achieved reduction in total cholesterol. Potential benefit from statin therapy may depend on degree of reduction achieved in total and LDL-cholesterol and adherence to therapy.

  10. Arc binary intensity modulated radiation therapy (AB IMRT)

    NASA Astrophysics Data System (ADS)

    Yang, Jun

    The state of the art Intensity Modulate Radiation Therapy (IMRT) has been one of the most significant breakthroughs in the cancer treatment in the past 30 years. There are two types of IMRT systems. The first system is the binary-based tomotherapy, represented by the Peacock (Nomos Corp) and Tomo unit (TomoTherapy Inc.), adopting specific binary collimator leafs to deliver intensity modulated radiation fields in a serial or helical fashion. The other uses the conventional dynamic multileaf collimator (MLC) to deliver intensity modulated fields through a number of gantry positions. The proposed Arc Binary IMRT attempts to deliver Tomo-like IMRT with conventional dynamic MLC and combines the advantages of the two types of IMRT techniques: (1) maximizing the number of pencil beams for better dose optimization, (2) enabling conventional linear accelerator with dynamic MLC to deliver Tomo-like IMRT. In order to deliver IMRT with conventional dynamic MLC in a binary fashion, the slice-by-slice treatment with limited slice thickness has been proposed in the thesis to accommodate the limited MLC traveling speed. Instead of moving the patient to subsequent treatment slices, the proposed method offsets MLC to carry out the whole treatment, slice by slice sequentially, thus avoid patient position error. By denoting one arc pencil beam set as a gene, genetic algorithm (GA) is used as the searching engine for the dose optimization process. The selection of GA parameters is a crucial step and has been studied in depth so that the optimization process will converge with reasonable speed. Several hypothetical and clinical cases have been tested with the proposed IMRT method. The comparison of the dose distribution with other commercially available IMRT systems demonstrates the clear advantage of the new method. The proposed Arc Binary Intensity Modulated Radiation Therapy is not only theoretically sound but practically feasible. The implementation of this method would expand the

  11. [Low persistence of simvastatin and ezetimibe fixed combination in the lipid lowering therapy].

    PubMed

    Simonyi, Gábor; Ferenci, Tamás

    2015-01-25

    Bevezetés: Jól ismert, hogy a magas koleszterinszint fontos módosítható cardiovascularis kockázati tényező. A lipidcsökkentő kezelés során a cardiovascularis kockázat csökkentése miatt fontos a betegek terápiahűsége. Célkitűzés: A szerzők célja a simvastatin/ezetimib szabad és fix kombinációk, illetve a leghatékonyabb statin, a rozuvastatin egyéves perzisztenciájának összehasonlítása volt. Módszer: Az Országos Egészségbiztosítási Pénztár vényforgalmi adataira támaszkodva 2012. október 1. és 2013. szeptember 30. között első alkalommal a simvastatin/ezetimib szabad és fix kombinációi és a rozuvastatinmonoterápia receptjeit kiváltó betegeket választották ki, akik az ezt megelőző egy évben hasonló hatóanyaggal végzett antilipaemiás terápiában nem részesültek. A perzisztenciagörbéket Kaplan–Meier-becsléssel határozták meg, 95%-os, log-skálán számolt pontonkénti konfidenciaintervallummal. Cenzoráltnak azokat a betegeket vették, akik a vizsgálat záró időpontjában is perzisztensek voltak. A görbék modellezéséhez félparaméteres eljárást, Cox-regressziót használtak, ahol az egyetlen – kategoriális – magyarázó változó a terápia volt; referenciacsoportnak a simvastatin/ezetimib fix kombinációt vették. Eredmények: A bevonási kritériumoknak összesen 204 699 beteg felelt meg. E betegek közül 10 030 beteg kezdett simvastatin/ezetimib szabad, 7613 beteg simvastatin/ezetimib fix, illetve 187 056 beteg rozuvastatinmonoterápiát. Az egyéves perzisztencia a simvastatin/ezetimib szabad kombináció esetében 10,97%, a simvastatin/ezetimib fix kombinációt szedőkben 24,35%, míg a rozuvastatinmonoterápián lévők esetében 30,47% volt. A simvastatin/ezetimib fix kombinációhoz képest a simvastatin/ezetimib szabad kombináció elhagyásának az esélye 73%-kal volt nagyobb (kockázatarány = 1,73 [95% konfidenciaintervallum: 1,61–1,85], p<0,0001), míg a rozuvastatiné 20%-kal volt alacsonyabb (kockázatarány = 0,80 [95% konfidenciaintervallum: 0,78–0,82], p<0,0001). A 360. napra számított átlagos perzisztencia a simvastatin/ezetimib szabad kombináció esetén 107 nap, a simvastatin/ezetimib fix kombináció szedésekor 164 nap, míg a rozuvastatint szedőknél 185 nap volt. Következtetések: Vizsgálatukban igazolták, hogy a simvastatin/ezetimib szabad és fix kombináció egyéves perzisztenciája szignifikánsan alacsonyabb a rozuvastatinéhoz képest. Orv. Hetil., 2015, 156(4), 141–145.

  12. [Lipid-lowering therapy and patient adherence in the MULTI GAP 2013 trial].

    PubMed

    Simonyi, Gábor

    2014-04-27

    Bevezetés: A dyslipidaemia ismert cardiovascularis kockázati tényező. A lipidterápiában a célértékek elérésének fontos tényezője a megfelelő betegadherencia. Célkitűzés: A MULTI GAP (MULTI Goal Attainment Problem) 2013-as vizsgálatban atheroscleroticus betegségben szenvedő betegek esetében a statinterápia adherenciájának és perzisztenciájának felmérése, amely részben a vizsgálatban részt vevő orvosok becslésén, illetve 319, a megelőző évben elvégzett MULTI GAP vizsgálatban részt vett beteg esetében az Országos Egészségbiztosítási Pénztár vénykiváltási adatbázisán alapult. Módszer: A MULTI GAP 2013 vizsgálatban standard, strukturált kérdőívek segítségével 1519 beteg adatai kerültek feldolgozásra. Az elemzésben kiértékelésre kerültek az egyes ellátási szinteken elért lipidértékek, a kezelőorvos által vélt betegadherencia, a 319 beteg Országos Egészségbiztosítási Pénztár vénykiváltási adataira támaszkodó valós adherencia, a kezelőorvosok elégedettsége a statinterápia eredményeivel, illetve az adherencia és a lipideredmények összevetése. Eredmények: Az elmúlt 7 év felméréseinek adatait is figyelembe véve előtérbe kerültek a hatékonyabb statinok; az atorvastatin és rozuvastatin alkalmazásának összesített aránya 49%-ról 83%-ra, azaz mintegy 70%-kal nőtt. A betegadherencia vonatkozásában kimutatták, hogy a 2,5 mmol/l alatti LDL-koleszterin-értékeket elért betegeknél az 1 év alatt kiváltott receptek száma mintegy nyolc gyógyszertári beváltást jelentett. Ehhez képest a 2,5 mmol/l feletti LDL-koleszterin-értékű csoportban a gyógyszerkiváltás lényegesen alacsonyabb volt (5,3 és 6,3 közötti). Éves szinten a 10–12 és a 7–9 gyógyszerkiváltás szignifikánsan alacsonyabb LDL-koleszterin-szintet jelentett a semennyit (0), illetve az 1–3 receptet éves szinten kiváltók csoportjaihoz képest. A kezelőorvosok által 100%-os perzisztenciájúnak értékelt betegek valódi perzisztenciája 74%-os volt az Országos Egészségbiztosítási Pénztár adatbázisa szerint, amely mintegy 25%-kal alacsonyabb, mint a valóság. A kezelőorvosok a lipidcsökkentő terápia adherenciáját a betegek mintegy felében ítélték 100%-nak, ezzel szemben az Országos Egészségbiztosítási Pénztár adatai 36%-ot mutattak. A jobb adherenciájú betegek (90–100%) nagyobb arányban (59,5%) értek el 2,5 mmol/l alatti LDL-koleszterin-értékeket, mint az alacsonyabb adherenciájúnak tartott betegek. A kezelőorvosok elégedettsége a lipidértékekkel a 4,5–6 mmol/l közötti összkoleszterin-értékű csoportban 69–80%-ig terjedt, azonban igen magas, 53–54%-os elégedettséget mutattak a 7 feletti összkoleszterin-szintű betegek csoportjában. Következtetések: A vizsgálat eredményei szerint a vélt adherencia lényegesen magasabb az Országos Egészségbiztosítási Pénztár adatain alapuló elemzéshez viszonyítva. Ugyanakkor a magas lipidértékű betegekkel szemben a kezelőorvosok megelégedettsége is igen magasnak bizonyult. Mindezek arra utalnak, hogy nemcsak a betegek, hanem az orvosok adherenciáját is javítani kell a lipidcsökkentő irányelvekhez. Orv. Hetil., 2014, 155(17), 669–675.

  13. Monitoring of lipids, enzymes, and creatine kinase in patients on lipid-lowering drug therapy.

    PubMed

    Wiklund, Olov; Pirazzi, Carlo; Romeo, Stefano

    2013-09-01

    A number of plasma lipid parameters have been used to estimate cardiovascular risk and to be targets for treatment to reduce risk. Most risk algorithms are based on total cholesterol (T-C) or low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and most intervention trials have targeted the LDL-C levels. Emerging measures, which in some cases may be better for risk calculation and as alternative treatment targets, are apolipoprotein B and non-HDL-C. Other lipid measures that may contribute in risk analysis are triglycerides (TG), lipoprotein(a), and lipoprotein-associated phospholipase A2. The primary treatment target in cardiovascular prevention is LDL-C, and potential alternative targets are apoB and non-HDL-C. In selected individuals at high cardiovascular (CV) risk, TG should be targeted, but HDL-C, Lp(a), and ratios such as LDL-C/HDL-C or apoB/apoAI are not recommended as treatment targets. Lipids should be monitored during titration to targets. Thereafter, lipids should be checked at least once a year or more frequently to improve treatment adherence if indicated. Monitoring of muscle and liver enzymes should be done before the start of treatment. In stable conditions during treatment, the focus should be on clinical symptoms that may alert muscle or liver complications. Routine measurement of CK or ALT is not necessary during treatment with statins.

  14. [Intensive therapy in complicated forms of purulent gestational pyelonephritis].

    PubMed

    Dovlatian, A A

    2008-01-01

    The experience with 65 cases of purulent gestational pyelonephritis (PGP) is reviewed. The efficacy of PGP intensive therapy depends on early surgical elimination of the source of bacteriemia and sepsis. Choice of the surgical technique should be based both on extension of destructive changes in the kidney and severity of the complications. In some cases it is necessary to perform nephrostomy with sanation of the pyonecrotic foci in the kidney, in the other--it is necessary to perform urgent nephrectomy. Three basic components of pre- and postoperative intensive care should be considered: antibacterial treatment, infusion-transfusion therapy and efferent detoxication. Etiotropic therapy is conducted with three antibiotics injected intravenously and intramuscularly to provide effective concentrations of the drugs in the blood, urine and affected organs. PGP medication is based on inhibitor-defended penicillines and cephalosporines of the third-forth generation. Combined use of these antibiotics is effective in 95% cases. If the condition is life-threatening, carbapenems, fluoroguinolones, aminoglycosides and metronidasol can be applied. Detoxication is provided by 24-h infusion of crystalloids, concentrated glucose solutions (10-20%) with insulin, transfusion of fresh frozen plasm, albumin, protein. Plasmapheresis accelerates recovery, diminished nephrectomy rate by 14% and obstetric complications 1.8 fold, enables physiological term of delivery (37-39 weeks) in significant reduction of postnatal complications. Lethal outcomes were absent.

  15. Planning and delivery of intensity-modulated radiation therapy.

    PubMed

    Yu, Cedric X; Amies, Christopher J; Svatos, Michelle

    2008-12-01

    Intensity modulated radiation therapy (IMRT) is an advanced form of external beam radiation therapy. IMRT offers an additional dimension of freedom as compared with field shaping in three-dimensional conformal radiation therapy because the radiation intensities within a radiation field can be varied according to the preferences of locations within a given beam direction from which the radiation is directed to the tumor. This added freedom allows the treatment planning system to better shape the radiation doses to conform to the target volume while sparing surrounding normal structures. The resulting dosimetric advantage has shown to translate into clinical advantages of improving local and regional tumor control. It also offers a valuable mechanism for dose escalation to tumors while simultaneously reducing radiation toxicities to the surrounding normal tissue and sensitive structures. In less than a decade, IMRT has become common practice in radiation oncology. Looking forward, the authors wonder if IMRT has matured to such a point that the room for further improvement has diminished and so it is pertinent to ask what the future will hold for IMRT. This article attempts to look from the perspective of the current state of the technology to predict the immediate trends and the future directions. This article will (1) review the clinical experience of IMRT; (2) review what we learned in IMRT planning; (3) review different treatment delivery techniques; and finally, (4) predict the areas of advancements in the years to come.

  16. Advances in endonasal low intensity laser irradiation therapy

    NASA Astrophysics Data System (ADS)

    Jiao, Jian-Ling; Liu, Timon C.; Liu, Jiang; Cui, Li-Ping; Liu, Song-hao

    2005-07-01

    Endonasal low intensity laser therapy (ELILT) began in China in 1998. Now in China it is widely applied to treat hyperlipidemia and brain diseases such as Alzheimer's disease, Parkinson's disease, insomnia, poststroke depression, intractable headache, ache in head or face, cerebral thrombosis, acute ischemic cerebrovascular disease, migraine, brain lesion and mild cognitive impairment. There are four pathways mediating EILILT, Yangming channel, autonomic nervous systems and blood cells. Two unhealth acupoints of Yangming channal inside nose might mediate the one as is low intensity laser acupuncture. Unbalance autonomic nervous systems might be modulated. Blood cells might mediate the one as is intravascular low intensity laser therapy. These three pathways are integrated in ELILT so that serum amyloid β protein, malformation rate of erythrocyte, CCK-8, the level of viscosity at lower shear rates and hematocrit, or serum lipid might decrease, and melanin production/SOD activity or β endorphin might increase after ELILT treatment. These results indicate ELILT might work, but it need to be verified by randomized placebo-controlled trial.

  17. Lifibrol as a model compound for a novel lipid-lowering mechanism of action.

    PubMed

    Berthold, Heiner K; Sudhop, Thomas; von Bergmann, Klaus; Gouni-Berthold, Ioanna

    2010-12-01

    Lifibrol is a potent lipid-lowering drug with an unknown mechanism of action. We investigated its effects on lipoprotein and sterol metabolism in normocholesterolemic male participants. Seven participants were treated for 4 weeks with 600 mg/d lifibrol and 9 with 40 mg/d pravastatin in a double-blind randomized parallel-group trial. Kinetic studies were performed at baseline and under acute and chronic treatment. Turnover of apolipoprotein B-100 was investigated with endogenous stable-isotope labeling, and kinetic parameters were derived by multicompartmental modeling. Lathosterol and cholesterol metabolism were investigated using mass isotopomer distribution analysis (MIDA) after [1-(13)C]acetate labeling. Carbon metabolism was investigated by calculating the total isotope incorporation into newly formed sterols and measuring the disposal of acetate by (13)CO(2) breath analysis. Total- and low-density lipoprotein (LDL) cholesterol decreased by 18% and 27% under lifibrol and by 17% and 28% under pravastatin, respectively, whereas very-low-density lipoprotein (VLDL) cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol did not change. Very-low-density lipoprotein apoB fractional synthesis and production increased under lifibrol but remained unchanged under pravastatin. Low-density lipoprotein apoB fractional synthesis and production increased under pravastatin but remained unchanged under lifibrol. Mass isotopomer distribution analysis indicated that both drugs decrease endogenous sterol synthesis after acute administration, but pravastatin had more powerful effects. Carbon-13 appearance in breath was higher during pravastatin than during lifibrol treatment. Mass isotopomer distribution analysis and carbon metabolism analysis indicated compartmentalization at the site of sterol synthesis, thus suggesting differential effects of the 2 drugs. Although having comparable lipid-lowering properties, lifibrol seems to have a mechanism of action

  18. Monitoring the use of lipid-lowering medication among persons with newly diagnosed diabetes: a nationwide register-based study

    PubMed Central

    Vehko, Tuulikki; Sund, Reijo; Arffman, Martti; Manderbacka, Kristiina; Ilanne-Parikka, Pirjo; Keskimäki, Ilmo

    2013-01-01

    Objectives To develop a register-based monitoring system to provide information on the use of lipid-lowering medication among persons with diabetes in different patient groups and by socioeconomic position. Design Longitudinal and register-based, before and after diabetes diagnosis. Setting Finnish population. Participants A total of 121 053 persons aged 30–79 years with a new diagnosis of diabetes during 2000–2006. The annual cohorts were divided at the time of diabetes diagnosis by coronary heart disease (CHD) status. Primary and secondary outcome measures Lipid-lowering medication purchases after diabetes diagnosis and prior to the diagnosis. Results According to the health insurance reimbursement data the use of lipid-lowering medication advanced rapidly among people with diabetes in the early 2000s in Finland. Of the patients diagnosed with diabetes in 2000 only one-fourth used lipid-lowering medication in 6–12 months after their diagnosis. For those diagnosed in 2006, the utilization rate was 46%. Among those with a history of CHD the use of medication was markedly higher; 51–58% in 2000 and 77–79% in 2006. Taking into account the increasing trend and measuring the independent effect of the diagnosis of diabetes on lipid-lowering medication, setting the diagnosis increased the use by 10–50%. Despite increasing overall utilisation rates, socioeconomic difference in the use of lipid-lowering medication remained throughout the study period. In particular, the lowest income quintile differed from other income groups and in 2006 its use of lipid-lowering medication remained approximately 10% points lower compared with the overall level. Conclusions The lipid-lowering medication is being applied in an increasing population of new diabetes cases; however, modelling the independent effect of the diagnosis of diabetes on lipid-lowering medication shows that the diagnosis increased use, but did not abolish socioeconomic differences. PMID:24189078

  19. Lipid lowering in patients with treatment-resistant hypertension: an analysis from the Treating to New Targets (TNT) trial.

    PubMed

    Bangalore, Sripal; Fayyad, Rana; Laskey, Rachel; DeMicco, David; Deedwania, Prakash; Kostis, John B; Messerli, Franz H

    2014-07-14

    Patients with resistant hypertension are at high risk for adverse cardiovascular events. Efforts have been focused on lowering the surrogate endpoint of blood pressure (BP) with scant focus on reduction of hard cardiovascular endpoints. However, whether or not intensive lipid lowering is beneficial for reducing the risk of cardiovascular events in this high-risk cohort is not known. We evaluated 10 001 patients with coronary artery disease and a low-density lipoprotein cholesterol level <130 mg/dL, randomized to atorvastatin 80 vs. 10 mg, enrolled in the Treating to New Targets trial. Treatment-resistant hypertension (TRH) was defined as BP ≥140 mmHg despite being on three antihypertensive agents or <140 mmHg on four or more agents. Subjects were followed up for a median duration of 4.9 years. The primary outcome was major cardiovascular events (composite of non-fatal myocardial infarction (MI), fatal coronary heart disease (CHD), resuscitated cardiac arrest, and stroke). Among the 10 001 patients in the trial, 1112 (11.1%) patients had TRH. Atorvastatin 80 mg, in patients with TRH, was associated with a significant reduction in the risk of the primary outcome (HR = 0.70; 95% CI 0.52-0.93; P = 0.01), driven largely by a significant reduction in CHD deaths (HR = 0.55; 95% CI 0.32-0.97; P = 0.04). In addition, atorvastatin 80 mg was associated with a reduction in major coronary events (HR = 0.67; 95% CI 0.49-0.93; P = 0.02), and any cardiovascular or coronary event and with a trend (P = 0.05) towards reduction in all-cause mortality (HR = 0.68; 95% CI 0.46-1.01) when compared with atorvastatin 10 mg. The results were similar when analysed for the two separate components of the TRH cohort. In subjects with TRH, intensive lipid lowering with atorvastatin 80 mg is associated with a significant reduction in cardiovascular events. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013. For permissions please email: journals.permissions@oup.com.

  20. [The doctor-patient relationship in intensive therapy].

    PubMed

    Szulc, Roman

    2008-01-01

    The doctor-patient and doctor-patient's family relationships require skills of interpersonal communication, which is particularly important in intensive therapy. Unfortunately, such skills are not routinely taught and inadequacies are enormous. Communication skills are essential for decision-making and outcomes of therapy. The communication-related education should be obligatory and include abilities to use the linguistic and extra-linguistic signs suitable for the given circumstances. The former ought to have linguistic, psychological and social effects. The latter should involve gestures, voice modulation, facial expressions or even silence, if need be. ITU patients and their families expect physicians to behave appropriately and to provide them with competent emotional support and cooperation.

  1. Intensity of continuous renal replacement therapy in acute kidney injury.

    PubMed

    Palevsky, Paul M

    2009-01-01

    The intensity of continuous renal replacement therapy (CRRT) is generally assessed on the basis of small solute clearance with dosing usually expressed in terms of total effluent volume per unit time (e.g., ml/kg/hour). Although several clinical trials have suggested an improvement in survival with higher doses of CRRT, results have not been consistent across all studies. The results of recent trials of intensity of CRRT are reviewed. The largest and most recent trials suggest that there is no additional benefit to using effluent flow rates in excess of 20 ml/kg/hour, although earlier studies suggested improved survival with doses of 35 to 45 ml/kg/hour.

  2. Linear algebraic methods applied to intensity modulated radiation therapy.

    PubMed

    Crooks, S M; Xing, L

    2001-10-01

    Methods of linear algebra are applied to the choice of beam weights for intensity modulated radiation therapy (IMRT). It is shown that the physical interpretation of the beam weights, target homogeneity and ratios of deposited energy can be given in terms of matrix equations and quadratic forms. The methodology of fitting using linear algebra as applied to IMRT is examined. Results are compared with IMRT plans that had been prepared using a commercially available IMRT treatment planning system and previously delivered to cancer patients.

  3. Prolonged intermittent renal replacement therapy in the intensive care unit.

    PubMed

    Bellomo, R; Baldwin, I; Fealy, N

    2002-12-01

    To present a review on the use of prolonged intermittent renal replacement therapy in the intensive care patient. Articles and abstracts reporting the use of renal replacement therapy. Standard intermittent haemodialysis (IHD) has significant shortcomings in the treatment of the acute renal failure (ARF) of critical illness. These shortcomings include haemodynamic instability, the need to remove excess fluid over a short period of time, the episodic nature of small solute control, the limited ability to achieve middle molecular weight solute control and the episodic nature of acid-base control. Over the last 20 years, these limitations have stimulated the evolution and increased application of continuous renal replacement therapy (CRRT) which provides major biochemical, biological and physiological advantages compared with IHD, although it remains unclear as to whether such advantages translate into a survival advantage. However, CRRT is technically demanding, requires supervision 24 hr per day and is often associated with the need for continuous anticoagulation, which, in some patients, might be undesirable. In some institutions, CRRT changes the nurse to patient ratio from 1:2 to 1:1, an alteration which has cost implications and might affect resource availability for other patients. Accordingly, techniques which prolong the duration of intermittent therapy and avoid the need for 24 hr treatment may offer "best value" in the management of ARF in the intensive care unit (ICU). These techniques will be referred to as prolonged intermittent renal replacement therapies (PIRRT) in this article. They are characterised by several fundamental principles: 1. Use of a modified or standard dialysis machines, 2. Use of diffusion, convection or any combination of the two, 3. Application of a decreased intensity of solute removal compared with IHD, 4. Extended duration of treatment beyond the typical 3 or 4 hr of standard IHD (hence the term prolonged) but not beyond an 8

  4. Coronary heart disease benefits from blood pressure and lipid-lowering.

    PubMed

    Sever, Peter S; Poulter, Neil R; Mastorantonakis, Stylianos; Chang, Choon Lan; Dahlof, Bjorn; Wedel, Hans

    2009-06-26

    We have reported the benefits of atorvastatin and of an amlodipine-based regimen on coronary heart disease (CHD) events in hypertensive patients in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). We report further analyses on the combined benefits of these interventions. 19,342 hypertensive patients were randomised to either an amlodipine or an atenolol-based regimen in the ASCOT Blood Pressure-Lowering Arm (BPLA). 10,305 subjects with total cholesterol Lipid-Lowering Arm (LLA). Estimates of CHD risk at baseline based on the Framingham algorithm were compared with observed and predicted event rates throughout ASCOT-LLA. Estimated baseline Framingham risk of CHD events was 22.8 per 1000 patient years. After 3.3 years, when the LLA was stopped, the actual CHD event rate had fallen to 4.8 per 1000 patient years--a reduction of 79% in those assigned amlodipine-based treatment and atorvastatin. CHD benefits associated with BP and lipid lowering were larger than predicted by previous observational and trial data. We estimate that compared with pre-trial treatment, treating about 55 patients with the amlodipine-based regimen and atorvastatin would prevent one CHD event per year.

  5. Lipid-lowering effects of farnesylquinone and related analogues from the marine-derived Streptomyces nitrosporeus.

    PubMed

    Liu, Dong; Yang, Aigang; Wu, Chongming; Guo, Peng; Proksch, Peter; Lin, Wenhan

    2014-11-15

    Bioassay-guided fractionation of the fermentation broth of Arctic Streptomyces nitrosporeus YBH10-5 resulted in the isolation of seven new compounds named nitrosporeunols A-G (1-7), together with seven known analogues (8-14). Their structures were determined based on extensive spectroscopic analysis. Compounds 1-14 were evaluated for the lowering lipid effects, while two compounds (10 and 12) remarkably decreased lipid levels including total cholesterol (TC) and triglycerides (TG) in HepG2 cells. Quantitative realtime PCR and Western blot indicated that farnesylquinone (12) increased the expression of the key proteins including peroxisome proliferator-activated receptor-α (PPARα), peroxisome proliferator-activated receptor-γ, and coactivator 1α (PGC-1α), as well as their downstream genes carnitine palmitoyltransterase-1 (CPT-1), acyl-coenzyme A oxidase 1 (ACOX), malonyl CoA decarboxylase 1 (MCD1), pyruvate dehydrogenase kinase 4 (PDK4), and cholesterol 7α -hydroxylase (CYP7A1). Luciferase assay showed that 12 increased the transcriptional activity of PPARα, while its lipid-lowering effect was abolished by PPARα inhibitor, MK886, in HepG2 cells. These findings suggested that 12 is a potent lipid-lowering agent which may decrease lipid levels through upregulation of PPARα pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Effect of media milling on lipid-lowering and antioxidant activities of chitosan.

    PubMed

    Zhang, Wei; Xia, Wenshui

    2015-01-01

    The effect of media milling on lipid-lowering and antioxidant activities of chitosan was studied in rats fed high-fat diets. Results showed that media-milled chitosan was more effective than chitosan in reducing body weight gain and liver fat accumulation of rats. Compared with chitosan, the reducing effects of media-milled chitosan on serum triacylglycerol (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were increased by 10.1, 7.5 and 10.2%, and liver TG and TC-reducing effects were increased by 16.2 and 14.6%, respectively. Rats fed media-milled chitosan showed decreased levels of free fatty acid (FFA) and thiobarbituric acid-reactive substances (TBARS) and increased superoxide dismutase (SOD) activity. The cholesterol and fat in feces of rats fed media-milled chitosan were higher than those of rats fed chitosan. These results suggested media milling enhanced the lipid-lowering and antioxidant activities of chitosan, and the reason might be partly due to its effect on strengthening the ability of chitosan in promoting fecal lipid excretions. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Segmentation and leaf sequencing for intensity modulated arc therapy

    SciTech Connect

    Gladwish, Adam; Oliver, Mike; Craig, Jeff; Chen, Jeff; Bauman, Glenn; Fisher, Barbara; Wong, Eugene

    2007-05-15

    A common method in generating intensity modulated radiation therapy (IMRT) plans consists of a three step process: an optimized fluence intensity map (IM) for each beam is generated via inverse planning, this IM is then segmented into discrete levels, and finally, the segmented map is translated into a set of MLC apertures via a leaf sequencing algorithm. To date, limited work has been done on this approach as it pertains to intensity modulated arc therapy (IMAT), specifically in regards to the latter two steps. There are two determining factors that separate IMAT segmentation and leaf sequencing from their IMRT equivalents: (1) the intrinsic 3D nature of the intensity maps (standard 2D maps plus the angular component), and (2) that the dynamic multileaf collimator (MLC) constraints be met using a minimum number of arcs. In this work, we illustrate a technique to create an IMAT plan that replicates Tomotherapy deliveries by applying IMAT specific segmentation and leaf-sequencing algorithms to Tomotherapy output sinograms. We propose and compare two alternative segmentation techniques, a clustering method, and a bottom-up segmentation method (BUS). We also introduce a novel IMAT leaf-sequencing algorithm that explicitly takes leaf movement constraints into consideration. These algorithms were tested with 51 angular projections of the output leaf-open sinograms generated on the Hi-ART II treatment planning system (Tomotherapy Inc.). We present two geometric phantoms and 2 clinical scenarios as sample test cases. In each case 12 IMAT plans were created, ranging from 2 to 7 intensity levels. Half were generated using the BUS segmentation and half with the clustering method. We report on the number of arcs produced as well as differences between Tomotherapy output sinograms and segmented IMAT intensity maps. For each case one plan for each segmentation method is chosen for full Monte Carlo dose calculation (NumeriX LLC) and dose volume histograms (DVH) are calculated

  8. Cost of lipid lowering in patients with coronary artery disease by case method learning.

    PubMed

    Kiessling, Anna; Zethraeus, Niklas; Henriksson, Peter

    2005-01-01

    This investigation was undertaken to study the costs of a Case Method Learning (CML)-supported lipid-lowering strategy in secondary prevention of coronary artery disease (CAD) in primary care. This prospective randomized controlled trial in primary care with an additional external specialist control group in Södertälje, Stockholm County, Sweden, included 255 consecutive patients with CAD. Guidelines were mailed to all general practitioners (GPs; n=54) and presented at a common lecture. GPs who were randomized to the intervention group participated in recurrent CML dialogues at their primary health-care centers during a 2-year period. A locally well-known cardiologist served as a facilitator. Assessment of low-density lipoprotein (LDL) cholesterol was performed at baseline and after 2 years. Analysis according to intention-to-treat-intervention and control groups (n=88)--was based on group affiliation at baseline. The marginal cost of lipid lowering comprised increased cost of lipid-lowering drugs in the intervention group compared with the primary care control group, cost of attendance of the GP's in the intervention group, and cost of time for preparation, travel, and seminars of the facilitator. Costs are as of 2002 with an exchange rate 1 U.S. dollar = 9.5 SEK (Swedish Crowns). Patients in the primary care intervention group had their LDL cholesterol reduced by 0.5 (confidence interval [CI], 0.1-0.9) mmol/L compared with the primary care control group (p < .05). No change occurred in controls. LDL cholesterol in the external specialist control group decreased by 0.6 (CI, 0.4-0.8) mmol/L. The cost of the educational intervention represented only 2 percent of the drug cost. The cost of lipid lowering in the intervention group, including the cost of the educational intervention, was actually lower than that of patients treated at the specialist clinic--106 U.S. dollar per mmol decrease in LDL cholesterol in the intervention group and 153 U.S. dollar per mmol

  9. [Hospital infections caused by Pseudomonas aeruginosa. Significance in intensive therapy].

    PubMed

    Sidorenko, S V; Gel'fand, E B; Mamontova, O A

    1999-01-01

    The significance of P. aeruginosa as an agent of hospital infections in intensive care departments is determined by high prevalence of this microorganism, its natural and acquired resistance to antibiotics of various groups, and severity of the infection it induces. The resistance of P. aeruginosa to antibiotics is different in different regions. Among the strains isolated in Moscow in intensive care wards for newborns 9% were resistant to meropenem, 10% to amicacine, 15% to imipramine, 16% to cefepime, 37% to ceftasidime, 45% to piperacylline/tasobactam, 45% to ciprofloxacine, and 60% to gentamicin; 1.5% of these strains were resistant to all tested antibiotics. High prevalence of antibiotic resistance among P. aeruginosa impedes the choice of drugs for empirical antibiotic therapy and increases the significance of microbiological diagnosis. Even if an agent is sensitive to such antibiotics as semisynthetic penicillines and aminoglycosides, their use as monotherapy in infections caused by P. aeruginosa is ineffective. Carbapenemes, III- IV generations cefalosporines, and fluoroquinolones can be used as mono therapy.

  10. Intensity-modulated arc therapy: principles, technologies and clinical implementation

    NASA Astrophysics Data System (ADS)

    Yu, Cedric X.; Tang, Grace

    2011-03-01

    Intensity-modulated arc therapy (IMAT) was proposed by Yu (1995 Phys. Med. Biol. 40 1435-49) as an alternative to tomotherapy. Over more than a decade, much progress has been made. The advantages and limitations of the IMAT technique have also been better understood. In recent years, single-arc forms of IMAT have emerged and become commercially adopted. The leading example is the volumetric-modulated arc therapy (VMAT), a single-arc form of IMAT that delivers apertures of varying weights with a single-arc rotation that uses dose-rate variation of the treatment machine. With commercial implementation of VMAT, wide clinical adoption has quickly taken root. However, there remains a lack of general understanding for the planning of such arc treatments, as well as what delivery limitations and compromises are made. Commercial promotion and competition add further confusion for the end users. It is therefore necessary to provide a summary of this technology and some guidelines on its clinical implementation. The purpose of this review is to provide a summary of the works from the radiotherapy community that led to wide clinical adoption, and point out the issues that still remain, providing some perspective on its further developments. Because there has been vast experience in IMRT using multiple intensity-modulated fields, comparisons between IMAT and IMRT are also made in the review within the areas of planning, delivery and quality assurance.

  11. [Renal replacement therapy in Intensive Care Units in Catalonia (Spain)].

    PubMed

    Aguirre-Bermeo, H; Tomasa, T; Navas, A; Xirgu, J; Catalán-Ibars, R M; Morillas, J; Cuartero, M; Manciño, J M; Roglán, A

    2015-01-01

    To assess the indications, settings and techniques used in renal replacement therapy (RRT) in Intensive Care Units (ICUs). A prospective, multicenter observational study was carried out. Intensive Care Units. All patients admitted to ICUs during the two-month study period in 2011 who required RRT. None. Patient demographic characteristics, baseline clinical data, RRT technique and materials used. Thirty-three patients were analyzed. RRT was started within the first 24hours after ICU admission in 17 of the 33 patients (52%). At the start of RRT, 18% of the patients (n=6) presented grade R on the RIFLE acute kidney injury (AKI) scale. The most common disorder associated with AKI was multiple organ dysfunction syndrome (64%; n=21). At the start of RRT, most patients (76%; n=25) presented hemodynamic instability, while the remaining 24% (n=8) were considered hemodynamically stable. The most common RRT technique in hemodynamically stable patients was continuous renal replacement therapy (CRRT) (63%; n=5). CRRT was the technique of choice in all 25 of the hemodynamically unstable patients (100%). Anticoagulation was used in 55% (n=18) of the patients. In most cases (61%, n=20), RRT was administered through the right femoral vein. In 84% (n=28) of the patients, the ultrafiltration effluent flow rate was ≤ 35ml/kg/h. The ICU physicians in this study followed current RRT guidelines. CRRT was preferred over intermittent renal replacement therapy, regardless of patient hemodynamic status. Copyright © 2013 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

  12. Prone breast intensity modulated radiation therapy: 5-year results.

    PubMed

    Osa, Etin-Osa O; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D; Formenti, Silvia C

    2014-07-15

    To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm(3), mean 19.65 cm(3). In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm(3), mean 1.59 cm(3). There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard 6-week radiation therapy with a

  13. Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

    SciTech Connect

    Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D.; Formenti, Silvia C.

    2014-07-15

    Purpose: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Methods and Materials: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Results: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm{sup 3}, mean 19.65 cm{sup 3}. In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm{sup 3}, mean 1.59 cm{sup 3}. There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Conclusions: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and

  14. Influence Of Low Intensity Laser Therapy On Diabetic Polyneuropathy

    NASA Astrophysics Data System (ADS)

    Abdel-Raoof, N. A.; Elnhas, N. G.; Elsayed, I. M.

    2011-09-01

    Diabetic peripheral neuropathy is a consequence of diabetes-mediated impairment of blood flow, and resultant hypoxia of nerves that may develop within 10 years of the onset of diabetes in 40-50% of people with type 1 or type 2 diabetes. Low Intensity Laser Therapy (LILT) has been advocated for the treatment of chronic pain disorders as blood flow is an important determinant for pain relief. Comparing the effect of Helium-Neon Laser therapy versus Infrared laser therapy on blood vessels diameter and flow as well as level of sensation for neuropathy. Twenty diabetic patients suffering from neuropathy were enrolled in the study with age 45-55 years. They were assigned randomly into two equal groups in number; Group A underwent an application of He-Neon laser while Group B underwent an application of Infrared laser. Both groups received laser for 2 months. Blood flow velocity, and blood vessel diameter were investigated by using duplex Doppler ultrasound and peripheral neuropathy parameters were investigated by Semmes-Weinstein monofilament assessment. The results revealed that He-Neon laser as well as Infrared laser groups showed significant improvement in blood flow velocity, blood vessel diameter & neuropathy tested parameters after treatment but there was no significance difference between the two types of LILT. LILT is a safe, non-invasive and drug free method for improving blood flow & sensation in patients suffering from diabetic polyneuropathy in addition to preventing one of the most threatening microvascular complications of diabetes.

  15. Randomized trial comparing exercise therapy, alternating cold and hot therapy, and low intensity laser therapy for chronic lumbar muscle strain

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoguang; Li, Jie; Liu, Timon Chengyi; Yuan, Jianqin; Luo, Qingming

    2008-12-01

    The purpose of this study was to compare the effects of exercise therapy, alternating cold and hot (ACH) therapy and low intensity laser (LIL) therapy in patients with chronic lumbar muscle strain (CLMS). Thirty-two patients were randomly allocated to four groups: exercise group, ACH group, LIL group, and combination group of exercise, ACH and LIL, eight in each group. Sixteen treatments were given over the course of 4 weeks. Lumbar muscle endurance, flexion and lateral flexion measures, visual analogue scale (VAS) and lumbar disability questionnaire (LDQ) were used in the clinical and functional evaluations before, immediately after, and 4 weeks after treatment. It was found that the values of endurance, VAS and LDQ in all groups were significantly improved from before to after treatment (P < 0.01). The combination group showed significantly larger reduction on pain level and functional disability than the other groups immediately and 4 weeks after treatment (P < 0.01). Pain level reduced significantly more in the ACH group than in the exercise group or the LIL group immediately and 4 weeks after treatment (P < 0.05). Lumbar muscle endurance and spinal ranges of motion in all groups were improved after treatment but there was no significant difference between any therapy groups. In conclusion, exercise therapy, ACH therapy and LIL therapy were effective in the treatment of CLMS. ACH therapy was more effective than exercise therapy or LIL therapy. The combination therapy of exercise, ACH and LIL had still better rehabilitative effects on CLMS.

  16. Effective policy initiatives to constrain lipid-lowering drug expenditure growth in South Korea

    PubMed Central

    2014-01-01

    Background The rapid growth of prescription drug expenditures is a major problem in South Korea. Accordingly, the South Korean government introduced a positive listing system in 2006. They also adopted various price reduction policies. Nevertheless, the total expenditure for lipid-lowering drugs have steadily increased throughout South Korea. The present study explores the factors that have influenced the increased expenditures of lipid-lowering drugs with a particular focus on the effects of statins in this process. Methods This paper investigates the National Health Insurance claims data for prescribed lipid-lowering drugs collected between January 1, 2005 and December 31, 2009. We specifically focused on statins and assessed the yearly variation of statin expenditure by calculating the increased rate of paired pharmaceutical expenditures over a 2 year period. Our study classified statins into three categories: new entrants, core medicines and exiting medicines. For core medicines, we further examined influencing factors such as price, amount of drugs consumed by volume, and prescription changes (substitutes for other drug). Results Statin expenditure showed an average annual increase of 25.7% between 2005 and 2009. Among the different statins, the expenditure of atorvastatin showed a 36.6% annual increase rate, which was the most dramatic among all statins. Also we divided expenditure for core medicines by the price factor, volume factor, and prescription change. The result showed that annual weighted average prices of individual drug decreased each year, which clearly showed that price influenced statin expenditure in a negative direction. The use of generic drugs containing the same active ingredient as name-brand drugs increased and negatively affected statin expenditure (Generic Mix effect). However, the use of relatively expensive ingredients within statin increase, Ingredient Mix effect contributed to increased statin expenditure (Ingredient Mix effect

  17. Comparison of intensity modulated x-ray therapy and intensity modulated proton therapy for selective subvolume boosting: a phantom study

    PubMed Central

    Flynn, R T; Barbee, D L; Mackie, T R; Jeraj, R

    2009-01-01

    Selective subvolume boosting can theoretically improve tumour control probability while maintaining normal tissue complication probabilities similar to those of uniform dose distributions. In this work the abilities of intensity modulated x-ray therapy (IMXT) and intensity modulated proton therapy (IMPT) to deliver boosts to multiple subvolumes of varying size and proximities are compared in a thorough phantom study. IMXT plans were created using the step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) methods. IMPT plans were created with the spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT) methods. IMPT-DGT is a generalization of the distal edge tracking method designed to reduce the number of proton beam spots required to deliver non-uniform dose distributions relative to IMPT-SS. The IMPT methods were delivered over both 180° and 360° arcs. The IMXT-SAS and IMPT-SS methods least and most optimally satisfied the non-uniform dose prescriptions, respectively. The IMPT delivery methods reduced normal tissue integral dose by a factor of about two relative to the IMXT delivery methods, regardless of the delivery arc. The IMPT-DGT method reduced the number of proton beam spots by a factor of about three relative to the IMPT-SS method. PMID:17921573

  18. 3D treatment planning and intensity-modulated radiation therapy.

    PubMed

    Purdy, J A

    1999-10-01

    Three-dimensional (3D) image-based treatment planning and new delivery technologies have spurred the implementation of external beam radiation therapy techniques, in which the high-dose region is conformed much more closely to the target volume than previously possible, thus reducing the volume of normal tissues receiving a high dose. This form of external beam irradiation is referred to as 3D conformal radiation therapy (3DCRT). 3DCRT is not just an add-on to the current radiation oncology process; it represents a radical change in practice, particularly for the radiation oncologist. Defining target volumes and organs at risk in 3D by drawing contours on CT images on a slice-by-slice basis, as opposed to drawing beam portals on a simulator radiograph, can be challenging, because radiation oncologists are generally not well trained in cross-sectional imaging. Currently, the 3DCRT approach will increase the time and effort required by physicians inexperienced with 3D treatment planning. Intensity-modulated radiation therapy (IMRT) is a more advanced form of 3DCRT, but there is considerable developmental work remaining. The instrumentation and methods used for IMRT quality assurance procedures and testing are not well established. Computer optimization cost functions are too simplistic, and thus time-consuming. Subjective plan evaluation by the radiation oncologist is still the norm. In addition, many fundamental questions regarding IMRT remain unanswered. For example, the radiobiophysical consequences of altered time-dose-fraction are unknown. Also, the fact that there is much greater dose heterogeneity for both the target and normal critical structures with IMRT compared to traditional irradiation techniques challenges current radiation oncology planning principles. However, this new process of planning and treatment delivery shows significant potential for improving the therapeutic ratio. In addition, while inefficient today, these systems, when fully developed

  19. Interpenetrating network hydrogel beads of carboxymethylcellulose and egg albumin for controlled release of lipid lowering drug.

    PubMed

    Boppana, Rashmi; Kulkarni, Raghavendra V; Mutalik, Srinivas S; Setty, C Mallikarjun; Sa, Biswanath

    2010-01-01

    Novel interpenetrating network hydrogel beads of sodium carboxymethylcellulose and egg albumin loaded with a lipid lowering drug, simvastatin, were prepared by ionotropic gelation and covalent cross-linking method. The IPN beads were characterized by differential scanning colorimetric analysis, X-ray diffractometry to understand the crystalline nature of the drug after entrapment into IPN matrix. Fourier transform infrared spectroscopy was used to find the chemical stability of drug in the polymer matrix and scanning electron microscopy was performed to study the surface morphology. The ionically cross-linked beads were capable of releasing drug up to 7 h, whereas the drug release was extended up to 12 h in case of dual cross-linked beads. The beads which were prepared with higher concentration of glutaraldehyde released the drug more slowly. The release data were fitted to an empirical equation to determine the transport mechanism, which indicated the non-Fickian trend for drug transport.

  20. Lipid lowering activity of hydrosoluble chitosan and association with Aloe vera L. and Brassica olearaceae L.

    PubMed

    Geremias, R; Pedrosa, R C; Locatelli, C; de Fávere, V T; Coury-Pedrosa, R; Laranjeira, M C M

    2006-04-01

    The lipid lowering activity of chitosan associated with Aloe vera L. or hydrosoluble chitosan with Brassica olearaceae L. has been studied in rats. In this study, rats were submitted to different treatments with hydrosoluble chitosan alone (4% diet), hydrosoluble chitosan associated with Aloe vera L. or hydrosoluble chitosan with Brassica olearaceae L. (1:4, 4% diet) for 35 days, to identify the formula with the highest hypolipaemic potential. The results showed that all treatments reduced blood lipid levels but that hydrosoluble chitosan associated with Brassica olearaceae L. proved most efficient, because it decreased the levels of total cholesterol, LDL-cholesterol, VLDL-cholesterol and triglycerides in blood serum. The overall results suggest that the hydrosoluble chitosan/Brassica olearaceae L. association is a therapeutic alternative for hyperlipidaemia, and in this way may contribute to the prevention of atherogenic processes.

  1. Muscle Mass and Body Fat in Relation to Cardiovascular Risk Estimation and Lipid-Lowering Eligibility.

    PubMed

    Lee, Kayoung

    2016-12-06

    This cross-sectional population-based study aimed to evaluate the relationships of muscle-mass and body-fat phenotypes to 10-yr risk of cardiovascular disease (CVD) events and eligibility for lipid management. Participants were Korean adults (N = 7315; 3163 men, 4152 women) aged 40-79 yr, free from stroke and coronary heart disease, who provided complete data for estimating 10-yr CVD risk and body composition during the Fifth Korea National Health and Nutrition Examination Survey (2009-2010). Four levels of combined muscle mass and body fat were determined using sex-specific quintiles of appendicular skeletal muscle mass divided by height squared, and sex-specific quintiles of total body fat percentage. Ten-year CVD risk was calculated using Pooled Cohort Equations and Framingham risk scores. Lipid-lowering medication eligibility was determined using American College of Cardiology/American Heart Association (ACC/AHA) and Adult Treatment Panel (ATP) III guidelines. Compared with the reference group, the risk of CVD events was higher in men with low muscle mass, high body fat, or the 2 factors combined. CVD risk was lower in women with low muscle mass, higher in women with high body fat, and nonsignificant in women with the 2 factors. Participants with low muscle mass and high body fat had higher odds for medication eligibility using the ACC/AHA guidelines but not the ATP III guidelines. Higher estimated 10-yr CVD risk was associated with combined phenotypes of low muscle mass and high fat in men but not in women. Also, the relationship of these phenotypes to lipid-lowering medication eligibility was guideline-specific.

  2. Effect of vitamin D on bioavailability and lipid lowering efficacy of simvastatin.

    PubMed

    Al-Asmari, Abdulrahman K; Ullah, Zabih; Al-Sabaan, Fahad; Tariq, Mohammad; Al-Eid, Ahmed; Al-Omani, Saud F

    2015-03-01

    The 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) inhibitors known as "statins" are widely prescribed for the management of dyslipidemia. In spite of their muscle toxicity, use of statins has alarmingly increased worldwide. A recent report suggests that vitamin D (VD) levels are closely associated with lipid lowering activity and muscular toxicity of statins. However, data are limited and inconclusive. The present study was undertaken to investigate the effect of VD supplementation on the bioavailability and lipid lowering effect of simvastatin (ST). Adult Sprague-Dawley male rats (250 ± 10 g) were divided into four groups including control, ST (100 mg/kg/day), VD (100 μg/kg/day) and ST + VD group, respectively. After the dosing period of 8 days the animals were sacrificed and the blood was collected for the analysis of ST, its active metabolite simvastatin acid (STA), total cholesterol, triglyceride and liver enzymes including aspartate transaminase and alanine transaminase. The result of this study showed a significant decrease in the level of cholesterol and triglyceride in ST alone treated group, whereas VD alone failed to alter the blood lipid levels. Concomitant treatment with VD produced significant decrease in the bioavailability of ST and STA. However, there was no significant difference in the level of cholesterol in ST alone and in ST + VD treated group. Our results on the liver enzyme suggest that ST alone or in combination with VD does not produce any hepatotoxicity. Further studies using VD along with various statins for a longer duration are suggested.

  3. The psychiatric aspects of cardiac intensive therapy: a review.

    PubMed

    Bowden, P

    1975-05-01

    The post cardiotomy state is typically delirious and although organic factors are important it is multi-determined. Cerebral ischaemia has been implicated in the development of psychological disorder after resuscitation but longer term neurotic disorders also occur. Affective disturbances, particularly depression, are associated with the coronary care experience. The following conditions are directly related to an increased incidence of psychological disorder: age, loss of sleep, sensory deprivation, stressful experiences, pre-operative morbidity (both physical and mental), the severity of both surgical trauma and the post-operative medical state. For both the staff who administer intensive therapy and the patient who receives it there are unique psychological hazards, the management of which depends largely on mutual understanding and support.

  4. [Dosimetric verification of the intensity modulated radiation therapy].

    PubMed

    Zhang, Yuhai; Gao, Yang

    2010-05-01

    To research the method of dosimetric verification of the intensity modulated radiation therapy (IMRT). The IMRT treatment plans were designed by Eclipse TPS and were implemented in Varian ClinacIX LA with 6MV X-ray. The absolute point doses were measured using a PTW 0.6 cc ion chamber with UNIDOS E dosimeter and the planes dose distributions were measured using PTW 2D-Array ion chamber in the phantom. The error between the measured dose and calculated dose in the interesting points was less than 3%. The points passed ratio was more than 90% in gamma analysis method (3 mm 13%) about the plane dose distribution verification. The method of dosimetric verification of IMRT is reliable and efficient in the implementation.

  5. Palliative intensity modulated radiation therapy for symptomatic adrenal metastasis.

    PubMed

    Mod, H; Patel, V

    2013-05-01

    Metastasis to the adrenal glands is quite common; especially from melanomas, breast, lung, renal and gastro-intestinal tumours. The most common tumour found in the adrenals in post mortem series is a metastatic tumour; incidence ranging from 13 to 27%. The diagnosis of adrenal metastasis is now more common and easier due to staging and subsequent follow up with Computed tomography /Magnetic resonance imaging and or positron emission tomography-computed tomography imaging studies. Most of the times these metastatic lesions are clinically occult and those that do have clinical symptoms complain of pain, nausea, vomiting and early satiety. We irradiated a patient of non small cell lung cancer with adrenal metastasis with palliative Intensity Modulated Radiation Therapy and achieved a good response in terms of pain relief, stable disease and no side effects of the treatment.

  6. Basic studies on intravascular low-intensity laser therapy

    NASA Astrophysics Data System (ADS)

    Liu, Timon Cheng-Yi; Duan, Rui; Wang, Shuang-Xi; Liu, Jiang; Cui, Li-Ping; Jin, Hua; Liu, Song-Hao

    2006-09-01

    Intravascular low intensity laser therapy (ILILT) was originally put forward in USA in 1982, but popularized in Russia in 1980s and in China in 1990s, respectively. A randomized placebo-controlled study has shown ILILT clinical efficacy in patients suffering from rheumatoid arthritis. As Chinese therapeutic applications of ILILT were the most widely in the world, its basic research, such as intracellular signal transduction research, blood research in vitro, animal blood research in vivo, human blood research in vivo and traditional Chinese medicine research, was also very progressive in China. Its basic studies will be reviewed in terms of the biological information model of photobiomodulation in this paper. ILILT might work in view of its basic studies, but the further randomized placebo-controlled trial and the further safety research should be done.

  7. Preliminary evidence of genetic determinants of adiponectin response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network.

    PubMed

    Aslibekyan, S; An, P; Frazier-Wood, A C; Kabagambe, E K; Irvin, M R; Straka, R J; Tiwari, H K; Tsai, M Y; Hopkins, P N; Borecki, I B; Ordovas, J M; Arnett, D K

    2013-10-01

    Adiponectin is an adipose-secreted protein that has been linked to changes in insulin sensitivity, high-density lipoprotein cholesterol levels, and inflammatory patterns. Although fenofibrate therapy can raise adiponectin levels, treatment response is heterogeneous and heritable, suggesting a role for genetic mediators. This is the first genome-wide association study of fenofibrate effects on circulating adiponectin. Plasma adiponectin was measured in participants of the Genetics of Lipid Lowering Drugs and Diet Network (n = 793) before and after a 3-week daily treatment with 160 mg of fenofibrate. Associations between variants on the Affymetrix Genome-Wide Human SNP Array 6.0 and adiponectin were assessed using mixed linear models, adjusted for age, sex, site, and family. We observed a statistically significant (P = 5 × 10⁻⁸) association between rs2384207 in 12q24, a region previously linked to several metabolic traits, and the fenofibrate-induced change in circulating adiponectin. Additionally, our genome-wide analysis of baseline adiponectin levels replicated the previously reported association with CDH13 and suggested novel associations with markers near the PCK1, ZBP1, TMEM18, and SCUBE1 genes. The findings from the single marker tests were corroborated in gene-based analyses. Biological pathway analyses suggested a borderline significant association between the EGF receptor signaling pathway and baseline adiponectin levels. We present preliminary evidence linking several biologically relevant genetic variants to adiponectin levels at baseline and in response to fenofibrate therapy. Our findings provide support for fine-mapping of the 12q24 region to investigate the shared biological mechanisms underlying levels of circulating adiponectin and susceptibility to metabolic disease. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

    PubMed

    Dhruva, Sanket S; Huang, Chenxi; Spatz, Erica S; Coppi, Andreas C; Warner, Frederick; Li, Shu-Xia; Lin, Haiqun; Xu, Xiao; Furberg, Curt D; Davis, Barry R; Pressel, Sara L; Coifman, Ronald R; Krumholz, Harlan M

    2017-07-01

    Randomized trials of hypertension have seldom examined heterogeneity in response to treatments over time and the implications for cardiovascular outcomes. Understanding this heterogeneity, however, is a necessary step toward personalizing antihypertensive therapy. We applied trajectory-based modeling to data on 39 763 study participants of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) to identify distinct patterns of systolic blood pressure (SBP) response to randomized medications during the first 6 months of the trial. Two trajectory patterns were identified: immediate responders (85.5%), on average, had a decreasing SBP, whereas nonimmediate responders (14.5%), on average, had an initially increasing SBP followed by a decrease. Compared with those randomized to chlorthalidone, participants randomized to amlodipine (odds ratio, 1.20; 95% confidence interval [CI], 1.10-1.31), lisinopril (odds ratio, 1.88; 95% CI, 1.73-2.03), and doxazosin (odds ratio, 1.65; 95% CI, 1.52-1.78) had higher adjusted odds ratios associated with being a nonimmediate responder (versus immediate responder). After multivariable adjustment, nonimmediate responders had a higher hazard ratio of stroke (hazard ratio, 1.49; 95% CI, 1.21-1.84), combined cardiovascular disease (hazard ratio, 1.21; 95% CI, 1.11-1.31), and heart failure (hazard ratio, 1.48; 95% CI, 1.24-1.78) during follow-up between 6 months and 2 years. The SBP response trajectories provided superior discrimination for predicting downstream adverse cardiovascular events than classification based on difference in SBP between the first 2 measurements, SBP at 6 months, and average SBP during the first 6 months. Our findings demonstrate heterogeneity in response to antihypertensive therapies and show that chlorthalidone is associated with more favorable initial response than the other medications. © 2017 American Heart Association, Inc.

  9. Residual cardiovascular risk in patients who received lipid-lowering treatment in a real-life setting: retrospective study

    PubMed Central

    Perrone, Valentina; Sangiorgi, Diego; Buda, Stefano; Degli Esposti, Luca

    2016-01-01

    Introduction The objective of this study was twofold: 1) to assess the residual cardiovascular (CV) risk among patients treated with statins according to guidelines and at the recommended dosages; and 2) to assess the difference, if any, in the frequency of CV events when patients were treated with other lipid-lowering agents alongside statins. Methods A retrospective observational study including one local health unit was conducted. Administrative databases were linked to laboratory test database in order to collect cholesterol values at baseline. Patients were included if they had filled at least one prescription for statins between January 1, 2009 and December 31, 2011; patients’ records were considered for a 12-month time span. Results A total of 27,330 patients treated with statins were included (50% male, mean age 68.0±11.5 years). Among them, 770 were treated with statins according to guidelines and at the recommended dosages and had a low density lipoprotein-cholesterol value below the therapeutic target. Nevertheless, the risk of myocardial infarction or stroke remained: incidence rates were 1.3±1.0 per patient per year for moderate CV risk, 4.1±2.6 for high risk, and 12.5±11.0 for very high risk. This incremental risk was confirmed further using the Cox model, by correcting for age, sex, use of antiplatelet and/or antihypertensive therapy, and adherence to treatment. As a second analysis, we compared, after a propensity score matching, patients extracted from the overall sample who were treated with fibrates. Based on the Cox model, patients on fibrates had a risk for myocardial infarction or stroke lower than patients on statins. Conclusion Among patients treated with statins according to guidelines and at the recommended dosages, a residual CV risk was observed. We concluded that intervention for managing residual CV risk during statin therapy should be implemented. PMID:27822076

  10. Assessment of ADRs associated with lipid-lowering agents recorded in the Department of Internal Medicine, University Hospital, Jena.

    PubMed

    Hippius, M; Farker, K; Helble, S; Hoffmann, A

    2002-03-01

    Drug-related illness is an important cause of admission to hospital. Little information is available regarding the frequency of ADRs caused by antilipidemic agents classified as HMG-CoA reductase inhibitors (statins). Treatment with statins has been associated with the occurrence of myopathy or liver toxicity in case reports. Recent lipid intervention studies have involved the implementation of lipid lowering therapy with HMG-CoA reductase inhibitors in cardiovascular risk management. Since January 1997 we have been involved in a study, the aim of which was to improve the spontaneous drug information reporting system in Germany. The study was supported by the German Federal Institute for Drugs and Medical Devices, the "Bundesinstitut für Arzneimittel und Medizinprodukte", Berlin BfArM. Between early 1997 and late 2000, as a result of this monitoring of ADRs, we analyzed all patient histories concerning therapy with statins. A total of 550 ADR patients were evaluated, (209 male, 341 female) with a mean age of 66.4 years. 27 (4.9%) of all patients had received statins (atorvastatin = 12, fluvastatin = 7, simvastatin as well as pravastatin = 3, lovastatin = 2). Only 2 of the 27 patients admitted to hospital for typical ADRs of statins such as skeletal muscle toxicity (e.g. myalgia, rhabdomyolysis) or disorders involving hepatic structure or function were receiving statins (atorvastatin). An increased risk of rhabdomyolysis has been reported in the case of several statins, following concomitant use with erythromycin, cyclosporine or itraconazole, all of which are potent inhibitors of CYP3A4 enzyme. But only 1 atorvastatin patient had received cyclosporine as a CYP3A4 inhibitor. After discontinuing medication, signs of intoxication disappeared. The antihyperlipidemic drugs available are generally safe and effective, and rate of ADRs is low if concomitant intake of other drugs and the differing pharmacokinetic profiles of the statins are considered.

  11. Low Intensity Laser Therapy Applied in the Healing of Wounds

    NASA Astrophysics Data System (ADS)

    Kahn, Fred; Matthews, Jeffrey

    2009-06-01

    Objective: The aim of this study was to determine the outcomes of Low Intensity Laser Therapy (LILT) on wound healing for patients presenting with pain, compromised neurological and physical function and tissue damage associated with vascular/diabetic ulcerations of the lower extremity. Methods: A retrospective case review of six patients treated with LILT (GaAlAs SLD, 660 nm, 750 mW, 3.6 J/cm2; GaAlAs SLD, 840 nm, 1,500 mW, 6.48 J/cm2; GaAlAs laser, 830 nm, 75 mW, 270 J/cm2) was conducted of clinical features including pain, measured by visual analogue scale (VAS), motor function, measured by range of motion (ROM) and visual outcome, measured by wound dimensions for six patients (n = 6; 5 males, 1 female; age = 67.83 years). Results: Significant progress with regard to alleviation of pain (ΔVAS = -5), improvements in motor function (ΔROM = +40%), epithelialization (wound closure rate = 3%/week) and complete wound closure was achieved. No recurrence of pathology at least one month post cessation of therapy was evident (x¯% reduction in wound area = 100%). Conclusions: LILT achieved consistent, effective and clear endpoints, was cost effective, created no adverse effects and ultimately led to the salvage of extremities.

  12. Bamboo Leaf Flavones and Tea Polyphenols Show a Lipid-lowering Effect in a Rat Model of Hyperlipidemia.

    PubMed

    Yang, C; Yifan, L; Dan, L; Qian, Y; Ming-yan, J

    2015-12-01

    At present, most of the lipid-lowering drugs are western medicines, which have a lot of adverse reactions. Zhucha, an age-old Uyghur medicine, is made up of bamboo leaves and tea (green tea), which has good efficacy and lipid-lowering effect. The purpose of this study was to undertake a pharmacodynamic examination of the optimal proportions of bamboo leaf flavones and tea polyphenols required to achieve lipid lowering in rats. A hyperlipidemia rat model was used to examine the lipid lowering effects of bamboo leaf flavones and tea polyphenols. Wistar rats were divided into 13 groups including one hyperlipidemia model group and 2 positive drug groups as well as experimental groups (9 groups dosed with different proportions of bamboo leaf flavones and tea polyphenols, the 3 dosages of bamboo leaf flavones were 75 mg/kg/d, 50 mg/kg/d and 25 mg/kg/d respectively, the 3 dosages of tea polyphenol were 750 mg/kg/d, 500 mg/kg/d and 250 mg/kg/d). The weight, the levels of triglyceride (TG) and high-density lipoprotein cholesterol (HDL) were determined. A high dose of bamboo leaf flavones (75 mg/kg/d) combined with a medium dose of tea polyphenols (500 mg/kg/d) was deemed to be optimal for achieving a lipid-lowering effect, the weight had the smallest increase and the level of TG and HDL was similar to positive control. The bamboo leaf flavones and tea polyphenols were mixed according to a certain proportion (1:6.7), and the mixture achieved a lipid-lowering effect and might prove to be useful as a natural lipid-lowering agent. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Pitfalls in normalization for intensity-modulated radiation therapy planning

    SciTech Connect

    Williams, Greg . E-mail: greg.williams@hci.utah.edu; Tobler, Matt; Leavitt, Dennis

    2005-01-01

    Three-dimensional (3D) treatment planning often involves complex combinations of beam energies, treatment fields, and beam modifying devices. Even when a plan is devised that meets many treatment-planning objectives, limitations in the planner's ability to further adjust beam characteristics may require the radiation dose prescription to be normalized to an isodose level that best covers the target volume. While these normalizations help meet the volume coverage goals, they also result in adjustment of the dose delivered to the normal tissues and must be carefully evaluated. Intensity-modulated radiation therapy (IMRT) treatment planning allows combinations of complex dose patterns, in order to achieve the desired treatment planning goals. These dose patterns are created by defining a set of treatment planning objectives and then allowing the treatment planning computer to create intensity patterns, through the use of moving multileaf collimation that will meet the requested goals. Often, when an IMRT treatment plan is created that meets many of the treatment planning goals but falls short of volume coverage requirements, the planner is tempted to apply normalization principles similar to those utilized with 3D treatment planning. Again, these normalizations help meet the volume coverage goals, but unlike 3D planning situations, may result in avoidable delivery of additional doses to the normal tissues. The focus of this study is to evaluate the effect of application of normalization for IMRT planning using multiple patient situations. Recommendations would favor re-optimization over normalization in most planning situations.

  14. Robust PET-guided intensity-modulated radiation therapy

    SciTech Connect

    Li, H.; Bissonnette, J. P.; Purdie, T.; Chan, T. C. Y.

    2015-08-15

    Purpose: Functional image guided intensity-modulated radiation therapy has the potential to improve cancer treatment quality by basing treatment parameters such as heterogeneous dose distributions information derived from imaging. However, such heterogeneous dose distributions are subject to imaging uncertainty. In this paper, the authors develop a robust optimization model to design plans that are desensitized to imaging uncertainty. Methods: Starting from the pretreatment fluorodeoxyglucose-positron emission tomography scans, the authors use the raw voxel standard uptake values (SUVs) as input into a series of intermediate functions to transform the SUV into a desired dose. The calculated desired doses were used as an input into a robust optimization model to generate beamlet intensities. For each voxel, the authors assume that the true SUV cannot be observed but instead resides in an interval centered on the nominal (i.e., observed) SUV. Then the authors evaluated the nominal and robust solutions through a simulation study. The simulation considered the effect of the true SUV being different from the nominal SUV on the quality of the treatment plan. Treatment plans were compared on the metrics of objective function value and tumor control probability (TCP). Results: Computational results demonstrate the potential for improvements in tumor control probability and deviation from the desired dose distribution compared to a nonrobust model while maintaining acceptable tissue dose. Conclusions: Robust optimization can help design treatment plans that are more stable in the presence of image value uncertainties.

  15. Lipid-lowering property of Clausena anisum-olens in hypercholesterolemic rats.

    PubMed

    Bautista, Anbel M; Tan, Mario A; Apostol, Jovencio M

    2017-12-01

    Clausena anisum-olens (Blanco) Merr. (Rutaceae) is a medicinal shrub which has been reported to have various pharmacological uses. No study regarding the effects of C. anisum-olens on cholesterol-lowering has been reported. The effects of the ethanol extract of C. anisum-olens leaves on the cholesterol level of hypercholesterolemic rats were evaluated. Acute oral toxicity of the extract (175, 550 and 2000 mg/kg) was determined using female Sprague-Dawley rats, as described in OECD 425 Main test guidelines. The lipid-lowering assay utilized 30 male Sprague-Dawley rats divided into five groups (A-E). Triton X-100 was administered to induce hypercholesterolemia. After hypercholesterolemia induction, oral treatment of Atorvastatin and crude ethanol extract was given daily to the treatment groups for 14 days. The total cholesterol, triglycerides, HDL and LDL were determined before induction, after induction, after first week of treatment and after second week of treatment. Acute oral toxicity showed the crude extract is nontoxic up to 2000 mg/kg. The lipid-lowering assay indicated reduction of serum cholesterol (87.21 ± 5.10 mg/dL), triglycerides (58.09 ± 4.10 mg/dL) and LDL (27.82 ± 4.11 mg/dL) for 200 mg/kw extract. Reduction in serum cholesterol (74.72 ± 3.64 mg/dL), triglycerides (52.79 ± 2.98 mg/dL) and LDL (12.06 ± 5.51 mg/dL) were observed for 400 mg/kg group. The result is comparable to Atorvastatin, which showed serum cholesterol (80.90 ± 9.72 mg/dL), triglycerides (55.94 ± 7.19 mg/dL) and LDL (22.09 ± 7.60 mg/dL) reduction. The crude extract of C. anisum-olens proved to be useful in lowering of cholesterol.

  16. Dosimetrically Triggered Adaptive Intensity Modulated Radiation Therapy for Cervical Cancer

    SciTech Connect

    Lim, Karen; Stewart, James; Kelly, Valerie; Xie, Jason; Brock, Kristy K.; Moseley, Joanne; Cho, Young-Bin; Fyles, Anthony; Lundin, Anna; Rehbinder, Henrik; Löf, Johan; Jaffray, David A.; Milosevic, Michael

    2014-09-01

    Purpose: The widespread use of intensity modulated radiation therapy (IMRT) for cervical cancer has been limited by internal target and normal tissue motion. Such motion increases the risk of underdosing the target, especially as planning margins are reduced in an effort to reduce toxicity. This study explored 2 adaptive strategies to mitigate this risk and proposes a new, automated method that minimizes replanning workload. Methods and Materials: Thirty patients with cervical cancer participated in a prospective clinical study and underwent pretreatment and weekly magnetic resonance (MR) scans over a 5-week course of daily external beam radiation therapy. Target volumes and organs at risk (OARs) were contoured on each of the scans. Deformable image registration was used to model the accumulated dose (the real dose delivered to the target and OARs) for 2 adaptive replanning scenarios that assumed a very small PTV margin of only 3 mm to account for setup and internal interfractional motion: (1) a preprogrammed, anatomy-driven midtreatment replan (A-IMRT); and (2) a dosimetry-triggered replan driven by target dose accumulation over time (D-IMRT). Results: Across all 30 patients, clinically relevant target dose thresholds failed for 8 patients (27%) if 3-mm margins were used without replanning. A-IMRT failed in only 3 patients and also yielded an additional small reduction in OAR doses at the cost of 30 replans. D-IMRT assured adequate target coverage in all patients, with only 23 replans in 16 patients. Conclusions: A novel, dosimetry-triggered adaptive IMRT strategy for patients with cervical cancer can minimize the risk of target underdosing in the setting of very small margins and substantial interfractional motion while minimizing programmatic workload and cost.

  17. Commissioning of Peacock System for intensity-modulated radiation therapy.

    PubMed

    Saw, C B; Ayyangar, K M; Thompson, R B; Zhen, W; Enke, C A

    2001-01-01

    The Peacock System was introduced to perform tomographic intensity-modulated radiation therapy (IMRT). Commissioning of the Peacock System included the alignment of the multileaf intensity-modulating collimator (MIMiC) to the beam axis, the alignment of the RTA device for immobilization, and checking the integrity of the CRANE for indexing the treatment couch. In addition, the secondary jaw settings, couch step size, and transmission through the leaves were determined. The dosimetric data required for the CORVUS planning system were divided into linear accelerator-specific and MIMiC-specific. The linear accelerator-specific dosimetric data were relative output in air, relative output in phantom, percent depth dose for a range of field sizes, and diagonal dose profiles for a large field size. The MIMiC-specific dosimetric data were the in-plane and cross-plane dose profiles of a small and a large field size to derive the penumbra fit. For each treatment unit, the Beam Utility software requires the data be entered into the CORVUS planning system in modular forms. These modules were treatment unit information, angle definition, configuration, gantry and couch angles range, dosimetry, results, and verification plans. After the appropriate machine data were entered, CORVUS created a dose model. The dose model was used to create known simple dose distribution for evaluation using the verification tools of the CORVUS. The planned doses for phantoms were confirmed using an ion chamber for point dose measurement and film for relative dose measurement. The planning system calibration factor was initially set at 1.0 and will be changed after data on clinical cases are acquired. The treatment unit was released for clinical use after the approval icon was checked in the verification plans module.

  18. Baseline characteristics of the diabetic participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

    PubMed

    Barzilay, J I; Jones, C L; Davis, B R; Basile, J N; Goff, D C; Ciocon, J O; Sweeney, M E; Randall, O S

    2001-04-01

    Hypertension (HTN) is a major risk factor for cardiovascular disease (CVD) in the setting of diabetes. There is no consensus on how best to treat hypertension among those with diabetes. Here we describe the characteristics of a cohort of hypertensive adults with diabetes who are part of a large prospective blood pressure study. This study will help clarify the treatment of HTN in the setting of diabetes. The Antihypertensive and Lipid-Lowering high-risk hypertensive participants, ages > or = 55 years, designed to determine whether the incidence of fatal and nonfatal coronary heart disease (CHD) and combined cardiovascular events (fatal and nonfatal CHD, revascularization surgery, angina pectoris, congestive heart failure, and stroke) differs between diuretic (chlorthalidone) treatment and three alternative antihypertensive therapies: a calcium channel blocker (amlodipine), an ACE inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). The planned follow-up is an average of 6 years, to be completed March 2002. There are 15,297 diabetic individuals in the ALLHAT study (36.0% of the entire cohort). Of these individuals, 50.2% are male, 39.4% are African-American, and 17.7% are Hispanic. Demographic and laboratory characteristics of the cohort are similar to those of other studies of the U.S. elderly population with HTN. The sample size has 42 and 93% confidence, treatments for the two study outcomes. The diabetic cohort in ALLHAT wil be able to provide valuable information about the treatment of hypertension in older diabetic patients at risk for incident CVD.

  19. Lipid-lowering treatment patterns among patients with type 2 diabetes mellitus with high cardiovascular disease risk

    PubMed Central

    Quek, Ruben G W; Fox, Kathleen M; Wang, Li; Li, Lu; Gandra, Shravanthi R; Wong, Nathan D

    2015-01-01

    Objective To examine real-world treatment patterns of lipid-lowering treatment and their possible associated intolerance and/or ineffectiveness among patients with type 2 diabetes mellitus initiating statins and/or ezetimibe. Research design and methods Adult (aged ≥18 years) patients diagnosed with type 2 diabetes who initiated statins and/or ezetimibe from January 1, 2007 to June 30, 2011 were retrospectively identified from the IMS LifeLink Pharmetrics Plus commercial claims database. Patients were further classified into 3 high-risk cohorts: (1) history of cardiovascular event (CVE); (2) two risk factors (age and hypertension); (3) aged ≥40 years. Patients had continuous health plan enrolment ≥1 year preindex and postindex date (statin and/or ezetimibe initiation date). Primary outcomes were index statin intensity, treatment modification(s), possible associated statin/non-statin intolerance and/or ineffectiveness issues (based on treatment modification type), and time-to-treatment modification(s). Analyses for each cohort were stratified by age groups (<65 and ≥65 years). Results A total of 9823 (history of CVE), 62 049 (2 risk factors), and 128 691 (aged ≥40 years) patients were included. Among patients aged <65 years, 81.4% and 51.8% of those with history of CVE, 75.6% and 44.4% of those with 2 risk factors, and 77.9% and 47.1% of those aged ≥40 years had ≥1 and 2 treatment modification(s), respectively. Among all patients, 23.2–28.4% had possible statin intolerance and/or ineffectiveness issues after accounting for second treatment modification (if any). Conclusions Among patients with type 2 diabetes with high cardiovascular disease risk, index statin treatment modifications that potentially imply possible statin intolerance and/or ineffectiveness were frequent. PMID:26435839

  20. High Intensity Laser Therapy (HILT) versus TENS and NSAIDs in low back pain: clinical study

    NASA Astrophysics Data System (ADS)

    Zati, Allesandro; Fortuna, Damiano; Valent, A.; Filippi, M. V.; Bilotta, Teresa W.

    2004-09-01

    Low back pain, caused by lumbar disc herniation, is prevalently treated with a conservative approach. In this study we valued the efficacy of High Intensity Laser Therapy (HILT), compared with accepted therapies such as TENS and NSAIDs. Laser therapy obtained similar results in the short term, but better clinical effect over time than TENS and NSAIDs. In conclusion high intensity laser therapy appears to be a interesting new treatment, worthy of further research.

  1. Intensity-Modulated Radiation Therapy in Childhood Ependymoma

    SciTech Connect

    Schroeder, Thomas M.; Chintagumpala, Murali; Okcu, M. Fatih; Chiu, J. Kam; Teh, Bin S.; Woo, Shiao Y.; Paulino, Arnold C.

    2008-07-15

    Purpose: To determine the patterns of failure after intensity-modulated radiation therapy (IMRT) for localized intracranial ependymoma. Methods and Materials: From 1994 to 2005, 22 children with pathologically proven, localized, intracranial ependymoma were treated with adjuvant IMRT. Of the patients, 12 (55%) had an infratentorial tumor and 14 (64%) had anaplastic histology. Five patients had a subtotal resection (STR), as evidenced by postoperative magnetic resonance imaging. The clinical target volume encompassed the tumor bed and any residual disease plus margin (median dose 54 Gy). Median follow-up for surviving patients was 39.8 months. Results: The 3-year overall survival rate was 87% {+-} 9%. The 3-year local control rate was 68% {+-} 12%. There were six local recurrences, all in the high-dose region of the treatment field. Median time to recurrence was 21.7 months. Of the 5 STR patients, 4 experienced recurrence and 3 died. Patients with a gross total resection had significantly better local control (p = 0.024) and overall survival (p = 0.008) than those with an STR. At last follow-up, no patient had developed visual loss, brain necrosis, myelitis, or a second malignancy. Conclusions: Treatment with IMRT provides local control and survival rates comparable with those in historic publications using larger treatment volumes. All failures were within the high-dose region, suggesting that IMRT does not diminish local control. The degree of surgical resection was shown to be significant for local control and survival.

  2. Monte Carlo dose verification for intensity-modulated arc therapy

    NASA Astrophysics Data System (ADS)

    Li, X. Allen; Ma, Lijun; Naqvi, Shahid; Shih, Rompin; Yu, Cedric

    2001-09-01

    Intensity-modulated arc therapy (IMAT), a technique which combines beam rotation and dynamic multileaf collimation, has been implemented in our clinic. Dosimetric errors can be created by the inability of the planning system to accurately account for the effects of tissue inhomogeneities and physical characteristics of the multileaf collimator (MLC). The objective of this study is to explore the use of Monte Carlo (MC) simulation for IMAT dose verification. The BEAM/DOSXYZ Monte Carlo system was implemented to perform dose verification for the IMAT treatment. The implementation includes the simulation of the linac head/MLC (Elekta SL20), the conversion of patient CT images and beam arrangement for 3D dose calculation, the calculation of gantry rotation and leaf motion by a series of static beams and the development of software to automate the entire MC process. The MC calculations were verified by measurements for conventional beam settings. The agreement was within 2%. The IMAT dose distributions generated by a commercial forward planning system (RenderPlan, Elekta) were compared with those calculated by the MC package. For the cases studied, discrepancies of over 10% were found between the MC and the RenderPlan dose calculations. These discrepancies were due in part to the inaccurate dose calculation of the RenderPlan system. The computation time for the IMAT MC calculation was in the range of 20-80 min on 15 Pentium-III computers. The MC method was also useful in verifying the beam apertures used in the IMAT treatments.

  3. [The intensive care gallbladder as shock organ: symptoms and therapy].

    PubMed

    Rimkus, C; Kalff, J C

    2013-03-01

    Acute acalculous cholecystitis (AAC) represents a severe disease in critically ill patients. The pathogenesis of acute necroinflammatory gallbladder disease is multifactorial and intensive care unit (ICU) patients show multiple risk factors. In addition AAC is difficult to diagnose because of the vague physical and non-specific technical findings. Only the combination of clinical and technical findings including the challenging physical examination of critically ill patients, laboratory results and ultrasound or computed tomography (CT) scan, will lead to the diagnosis. The condition of AAC has a rapid progress to gallbladder necrosis, gangrene and perforation and these complications are reflected in the high morbidity and mortality rates, therefore, therapy should be promptly initiated. If there are no clinical contraindications for an operative approach cholecystectomy is the definitive treatment and both open and laparoscopic procedures have been used. In unstable, critically ill patients percutaneous cholecystostomy should be immediately performed. In addition, transpapillary endoscopic drainage is also possible if there are contraindications for percutaneous cholecystostomy. Patients who fail to improve or deteriorate following interventional drainage should be reconsidered for cholecystectomy. Due to the fact that more than 90 % of patients treated with percutaneous cholecystostomy showed no recurrence of symptoms during a period of more than 1 year, it is still unclear if percutaneous cholecystostomy is the definitive treatment of AAC for unstable patients or if delayed cholecystectomy is still necessary.

  4. Intensity modulated radiation therapy for breast cancer: current perspectives

    PubMed Central

    Buwenge, Milly; Cammelli, Silvia; Ammendolia, Ilario; Tolento, Giorgio; Zamagni, Alice; Arcelli, Alessandra; Macchia, Gabriella; Deodato, Francesco; Cilla, Savino; Morganti, Alessio G

    2017-01-01

    Background Owing to highly conformed dose distribution, intensity modulated radiation therapy (IMRT) has the potential to improve treatment results of radiotherapy (RT). Postoperative RT is a standard adjuvant treatment in conservative treatment of breast cancer (BC). The aim of this review is to analyze available evidence from randomized controlled trials (RCTs) on IMRT in BC, particularly in terms of reduction of side effects. Methods A literature search of the bibliographic database PubMed, from January 1990 through November 2016, was performed. Only RCTs published in English were included. Results Ten articles reporting data from 5 RCTs fulfilled the selection criteria and were included in our review. Three out of 5 studies enrolled only selected patients in terms of increased risk of toxicity. Three studies compared IMRT with standard tangential RT. One study compared the results of IMRT in the supine versus the prone position, and one study compared standard treatment with accelerated partial breast IMRT. Three studies reported reduced acute and/or late toxicity using IMRT compared with standard RT. No study reported improved quality of life. Conclusion IMRT seems able to reduce toxicity in selected patients treated with postoperative RT for BC. Further analyses are needed to better define patients who are candidates for this treatment modality. PMID:28293119

  5. The JUPITER lipid lowering trial and vitamin D: Is there a connection?

    PubMed

    Ware, William R

    2010-04-01

    There is growing evidence that vitamin D deficiency significantly increases the risk of adverse cardiovascular events and that a vitamin D status representing sufficiency or optimum is protective. Unfortunately, in clinical trials that address interventions for reducing risk of adverse cardiovascular events, vitamin D status is not generally measured. Failure to do this has now assumed greater importance with the report of a study that found rosuvastatin at doses at the level used in a recent large randomized lipid lowering trial (JUPITER) had a large and significant impact on vitamin D levels as measured by the metabolite 25-hydroxyvitamin D. The statin alone appears to have increased this marker such that the participants on average went from deficient to sufficient in two months. The difference in cardiovascular risk between those deficient and sufficient in vitamin D in observational studies was similar to the risk reduction found in JUPITER. Thus it appears that this pleiotropic effect of rosuvastatin may be responsible for part of its unusual effectiveness in reducing the risk of various cardiovascular endpoints found in JUPITER and calls into question the interpretation based only on LDL cholesterol and CRP changes. In addition, vitamin D status is a cardiovascular risk factor which up until now has not been considered in adjusting study results or in multivariate analysis, and even statistical analysis using only baseline values may be inadequate.

  6. Lipid lowering effects of iodothyronines: In vivo and in vitro studies on rat liver

    PubMed Central

    Vergani, Laura

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) is emerging as one of the most common liver diseases, leading to the increasing interest for new therapeutic approaches for its treatment. NAFLD primarily depends on a hypercaloric and/or unbalanced diet leading to overweight and obesity. The liver, in fact, plays a central role in lipid metabolism by importing free fatty acids from the blood and synthesizing, storing, oxidizing and exporting lipids. Furthermore, the liver is the target for the thyroid hormones, thyroxine (T4) and 3,3’,5-triiodo-L-thyronine (T3), that stimulate the basal metabolic rate and lead to body weight loss. In the last decade, other iodothyronines have been shown to possess biological relevance and play some thyromimetic activities; in particular, 3,5-diiodo-L-thyronine (T2) gained large interest. The global effect of iodothyronines on liver lipid metabolism results from the balance between direct and indirect actions on the hepatocyte, leading to stimulation of lipid synthesis, oxidation and autophagy. In this review, the results so far obtained on both in vivo and in vitro models of hepatosteatosis are summarized in order to obtain an updated picture of the lipid-lowering effects of iodothyronines on mammalian liver. PMID:24799985

  7. Role of lipid-lowering agents in the management of diabetic retinopathy

    PubMed Central

    Ioannidou, Estelle; Tseriotis, Vasilis-Spyridon; Tziomalos, Konstantinos

    2017-01-01

    Diabetic retinopathy affects a substantial proportion of patients with diabetes mellitus (DM) and is the leading cause of blindness in working-aged adults. Even though the incidence of diabetic retinopathy has declined in the last decades, its prevalence increased and is expected to rise further as a result of the increasing incidence of type 2 DM (T2DM) and the longer life expectancy of patients with DM. The pathogenesis of diabetic retinopathy is multifactorial. Some observational studies suggested an association between dyslipidemia and the development and progression of retinopathy in patients with DM but others did not confirm this association. Regarding lipid-lowering agents, studies that evaluated the role of statins in the management of these patients are mostly small and yielded discrepant results. Large randomized studies with statins in patients with T2DM showed no benefit of these agents on diabetic retinopathy but were not designed to address this effect. In contrast, both preclinical data and two large randomized controlled studies, the FIELD and the ACCORD trial, showed that fenofibrate delays the progression of diabetic retinopathy. Even though the mechanisms underpinning this favorable effect are not entirely clear, these findings suggest that fenofibrate might represent a useful tool for the management of diabetic retinopathy. PMID:28138358

  8. Lipid-lowering Activity of Natural and Semi-Synthetic Sterols and Stanols.

    PubMed

    Taha, Dhiaa A; Wasan, Ellen K; Wasan, Kishor M; Gershkovich, Pavel

    2015-01-01

    Consumption of plant sterols/ stanols has long been demonstrated to reduce plasma cholesterol levels. The objective of this review is to demonstrate the lipid-lowering activity and anti-atherogenic effects of natural and semi-synthetic plant sterols/ stanols based on evidence from cell-culture studies, animal studies and clinical trials. Additionally, this review highlights certain molecular mechanisms by which plant sterols/ stanols lower plasma cholesterol levels with a special emphasis on factors that affect the cholesterol-lowering activity of plant sterols/stanols. The crystalline nature and the poor oil solubility of these natural products could be important factors that limit their cholesterol-lowering efficiency. Several attempts have been made to improve the cholesterol-lowering activity by enhancing the bioavailability of crystalline sterols and stanols. Approaches involved reduction of the crystal size and/or esterification with fatty acids from vegetable or fish oils. However, the most promising approach in this context is the chemical modification of plant sterols /stanols into water soluble disodium ascorbyl phytostanyl phosphates analogue by esterification with ascorbic acid. This novel semi-synthetic stanol derivative has improved efficacy over natural plant sterols/ stanols and can provide additional benefits by combining the cholesterol-lowering properties of plant stanols with the antioxidant potential of ascorbic acid. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

  9. Lipid-lowering drugs associated with slower motor decline in the elderly adults.

    PubMed

    Dumurgier, Julien; Singh-Manoux, Archana; Tavernier, Béatrice; Tzourio, Christophe; Elbaz, Alexis

    2014-02-01

    Vascular risk factors contribute to motor decline in the elderly persons. We investigated the relationship between lipid-lowering drugs (LLDs) use and decline in walking speed (WS) in older adults. Data on 4,009 community-dwelling men and women, aged ≥65 years at baseline, are drawn from the Dijon (France) center of the Three-City study. "Fast" WS was assessed over 6 m at baseline and at 4, 6, 8, and 10 years of follow-up. Mixed linear models were used to determine the relationship between LLDs and change in WS over the follow-up. At baseline, 1,295 (32%) participants used LLDs (statins, n = 643; fibrates, n = 652); mean fast WS was 152.9cm/s and not significantly different between LLDs users and nonusers. In models adjusted for age, sex, cholesterol level, and other covariates, WS decline was 25% slower in LLDs users (difference with nonusers: 0.58cm/s/y, 95% CI: 0.30, 0.86; p < .001). Both fibrates and statins were associated with slower decline, but only the effect of statins was robust in analyses that took missing values into account. The beneficial effect was more pronounced in those on LLDs continuously over the follow-up. Fast WS declined less in those on LLDs, suggesting that the effect of LLDs, statins in particular, extend beyond that on cardiovascular disease in the elderly persons. However, these effects were modest and their clinical relevance is unclear.

  10. Are high coronary risk patients missing out on lipid-lowering drugs in Australia?

    PubMed

    Simons, Leon A; Chung, Eric

    2014-08-18

    To examine whether high coronary risk patients in Australia, where use of lipid-lowering drugs (LLD) is very high by international standards, are receiving LLD. Assessment of Pharmaceutical Benefits Scheme pharmacy payment claim records between January 2006 and May 2013 for a 10% random sample of Australian concession card holders. Co-prescriptions were used as a surrogate for high coronary risk groups - coronary heart disease (CHD): antiplatelet drugs (not including solo aspirin) and anti-anginal drugs; diabetes: all standard drugs; hypertension: all standard drugs (not including solo diuretics). Proportions of patients in high-risk groups not receiving LLD (statins, fibrates or ezetimibe). The database yielded information on 276,212 patients defined as being at high coronary risk (mean age, 66.1 [SD, 14.8] years; 44% male). Of this group, 115,477 patients (42%) had not received any LLD during the study period. For patients in the risk group for CHD in combination with diabetes and hypertension, only 8% (1111/14,257) were not receiving LLD. Across all risk groups, the proportions not receiving LLD were generally highest in those aged ≥ 81 years and, to a lesser extent, < 41 years, and were lowest in those aged 51-70 years. A large proportion of concession card holders at high coronary risk, especially those in middle age with CHD and multiple risk factors, are being appropriately prescribed LLD in Australia.

  11. Intensive insulin therapy in mixed medical/surgical intensive care units: benefit versus harm.

    PubMed

    Van den Berghe, Greet; Wilmer, Alexander; Milants, Ilse; Wouters, Pieter J; Bouckaert, Bernard; Bruyninckx, Frans; Bouillon, Roger; Schetz, Miet

    2006-11-01

    Intensive insulin therapy (IIT) improves the outcome of prolonged critically ill patients, but concerns remain regarding potential harm and the optimal blood glucose level. These questions were addressed using the pooled dataset of two randomized controlled trials. Independent of parenteral glucose load, IIT reduced mortality from 23.6 to 20.4% in the intention-to-treat group (n = 2,748; P = 0.04) and from 37.9 to 30.1% among long stayers (n = 1,389; P = 0.002), with no difference among short stayers (8.9 vs. 10.4%; n = 1,359; P = 0.4). Compared with blood glucose of 110-150 mg/dl, mortality was higher with blood glucose >150 mg/dl (odds ratio 1.38 [95% CI 1.10-1.75]; P = 0.007) and lower with <110 mg/dl (0.77 [0.61-0.96]; P = 0.02). Only patients with diabetes (n = 407) showed no survival benefit of IIT. Prevention of kidney injury and critical illness polyneuropathy required blood glucose strictly <110 mg/day, but this level carried the highest risk of hypoglycemia. Within 24 h of hypoglycemia, three patients in the conventional and one in the IIT group died (P = 0.0004) without difference in hospital mortality. No new neurological problems occurred in survivors who experienced hypoglycemia in intensive care units (ICUs). We conclude that IIT reduces mortality of all medical/surgical ICU patients, except those with a prior history of diabetes, and does not cause harm. A blood glucose target <110 mg/day was most effective but also carried the highest risk of hypoglycemia.

  12. Intensive Versus Distributed Aphasia Therapy: A Nonrandomized, Parallel-Group, Dosage-Controlled Study.

    PubMed

    Dignam, Jade; Copland, David; McKinnon, Eril; Burfein, Penni; O'Brien, Kate; Farrell, Anna; Rodriguez, Amy D

    2015-08-01

    Most studies comparing different levels of aphasia treatment intensity have not controlled the dosage of therapy provided. Consequently, the true effect of treatment intensity in aphasia rehabilitation remains unknown. Aphasia Language Impairment and Functioning Therapy is an intensive, comprehensive aphasia program. We investigated the efficacy of a dosage-controlled trial of Aphasia Language Impairment and Functioning Therapy, when delivered in an intensive versus distributed therapy schedule, on communication outcomes in participants with chronic aphasia. Thirty-four adults with chronic, poststroke aphasia were recruited to participate in an intensive (n=16; 16 hours per week; 3 weeks) versus distributed (n=18; 6 hours per week; 8 weeks) therapy program. Treatment included 48 hours of impairment, functional, computer, and group-based aphasia therapy. Distributed therapy resulted in significantly greater improvements on the Boston Naming Test when compared with intensive therapy immediately post therapy (P=0.04) and at 1-month follow-up (P=0.002). We found comparable gains on measures of participants' communicative effectiveness, communication confidence, and communication-related quality of life for the intensive and distributed treatment conditions at post-therapy and 1-month follow-up. Aphasia Language Impairment and Functioning Therapy resulted in superior clinical outcomes on measures of language impairment when delivered in a distributed versus intensive schedule. The therapy progam had a positive effect on participants' functional communication and communication-related quality of life, regardless of treatment intensity. These findings contribute to our understanding of the effect of treatment intensity in aphasia rehabilitation and have important clinical implications for service delivery models. © 2015 American Heart Association, Inc.

  13. Simultaneous beam geometry and intensity map optimization in intensity-modulated radiation therapy.

    PubMed

    Lee, Eva K; Fox, Tim; Crocker, Ian

    2006-01-01

    In current intensity-modulated radiation therapy (IMRT) plan optimization, the focus is on either finding optimal beam angles (or other beam delivery parameters such as field segments, couch angles, gantry angles) or optimal beam intensities. In this article we offer a mixed integer programming (MIP) approach for simultaneously determining an optimal intensity map and optimal beam angles for IMRT delivery. Using this approach, we pursue an experimental study designed to (a) gauge differences in plan quality metrics with respect to different tumor sites and different MIP treatment planning models, and (b) test the concept of critical-normal-tissue-ring--a tissue ring of 5 mm thickness drawn around the planning target volume (PTV)--and its use for designing conformal plans. Our treatment planning models use two classes of decision variables to capture the beam configuration and intensities simultaneously. Binary (0/1) variables are used to capture "on" or "off" or "yes" or "no" decisions for each field, and nonnegative continuous variables are used to represent intensities of beamlets. Binary and continuous variables are also used for each voxel to capture dose level and dose deviation from target bounds. Treatment planning models were designed to explicitly incorporate the following planning constraints: (a) upper/lower/mean dose-based constraints, (b) dose-volume and equivalent-uniform-dose (EUD) constraints for critical structures, (c) homogeneity constraints (underdose/overdose) for PTV, (d) coverage constraints for PTV, and (e) maximum number of beams allowed. Within this constrained solution space, five optimization strategies involving clinical objectives were analyzed: optimize total intensity to PTV, optimize total intensity and then optimize conformity, optimize total intensity and then optimize homogeneity, minimize total dose to critical structures, minimize total dose to critical structures and optimize conformity simultaneously. We emphasize that the

  14. Low intensity laser therapy accelerates muscle regeneration in aged rats

    PubMed Central

    Vatansever, Fatma; Rodrigues, Natalia C.; Assis, Livia L.; Peviani, Sabrina S.; Durigan, Joao L.; Moreira, Fernando M.A.; Hamblin, Michael R.; Parizotto, Nivaldo A.

    2013-01-01

    Background Elderly people suffer from skeletal muscle disorders that undermine their daily activity and quality of life; some of these problems can be listed as but not limited to: sarcopenia, changes in central and peripheral nervous system, blood hypoperfusion, regenerative changes contributing to atrophy, and muscle weakness. Determination, proliferation and differentiation of satellite cells in the regenerative process are regulated by specific transcription factors, known as myogenic regulatory factors (MRFs). In the elderly, the activation of MRFs is inefficient which hampers the regenerative process. Recent studies found that low intensity laser therapy (LILT) has a stimulatory effect in the muscle regeneration process. However, the effects of this therapy when associated with aging are still unknown. Objective This study aimed to evaluate the effects of LILT (λ=830 nm) on the tibialis anterior (TA) muscle of aged rats. Subjects and methods The total of 56 male Wistar rats formed two population sets: old and young, with 28 animals in each set. Each of these sets were randomly divided into four groups of young rats (3 months of age) with n=7 per group and four groups of aged rats (10 months of age) with n=7 per group. These groups were submitted to cryoinjury + laser irradiation, cryoinjury only, laser irradiation only and the control group (no cryoinjury/no laser irradiation). The laser treatment was performed for 5 consecutive days. The first laser application was done 24 h after the injury (on day 2) and on the seventh day, the TA muscle was dissected and removed under anesthesia. After this the animals were euthanized. Histological analyses with toluidine blue as well as hematoxylin-eosin staining (for counting the blood capillaries) were performed for the lesion areas. In addition, MyoD and VEGF mRNA was assessed by quantitative polymerase chain reaction. Results The results showed significant elevation (p<0.05) in MyoD and VEGF genes expression levels

  15. Prioritized efficiency optimization for intensity modulated proton therapy.

    PubMed

    Müller, Birgit S; Wilkens, Jan J

    2016-12-07

    A high dosimetric quality and short treatment time are major goals in radiotherapy planning. Intensity modulated proton therapy (IMPT) plans obtain dose distributions of great conformity but often result in long delivery times which are typically not incorporated into the optimization process. We present an algorithm to optimize delivery efficiency of IMPT plans while maintaining plan quality, and study the potential trade-offs of these interdependent objectives. The algorithm is based on prioritized optimization, a stepwise approach to implemented objectives. First the quality of the plan is optimized. The second step of the prioritized efficiency optimization (PrEfOpt) routine offers four alternatives for reducing delivery time: minimization of the total spot weight sum (A), maximization of the lowest spot intensity of each energy layer (B), elimination of low-weighted spots (C) or energy layers (D). The trade-off between dosimetric quality (step I) and treatment time (step II) is controlled during the optimization by option-dependent parameters. PrEfOpt was applied to a clinical patient case, and plans for different trade-offs were calculated. Delivery times were simulated for two virtual facilities with constant and variable proton current, i.e. independent and dependent on the optimized spot weight distributions. Delivery times decreased without major degradation of plan quality; absolute time reductions varied with the applied method and facility type. Minimizing the total spot weight sum (A) reduced times by 28% for a similar plan quality at a constant current (changes of minimum dose in the target  <1%). For a variable proton current, eliminating low-weighted spots (C) led to remarkably faster delivery (16%). The implementation of an efficiency-optimization step into the optimization process can yield reduced delivery times with similar plan qualities. A potential clinical application of PrEfOpt is the generation of multiple plans with different trade

  16. Prioritized efficiency optimization for intensity modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Müller, Birgit S.; Wilkens, Jan J.

    2016-12-01

    A high dosimetric quality and short treatment time are major goals in radiotherapy planning. Intensity modulated proton therapy (IMPT) plans obtain dose distributions of great conformity but often result in long delivery times which are typically not incorporated into the optimization process. We present an algorithm to optimize delivery efficiency of IMPT plans while maintaining plan quality, and study the potential trade-offs of these interdependent objectives. The algorithm is based on prioritized optimization, a stepwise approach to implemented objectives. First the quality of the plan is optimized. The second step of the prioritized efficiency optimization (PrEfOpt) routine offers four alternatives for reducing delivery time: minimization of the total spot weight sum (A), maximization of the lowest spot intensity of each energy layer (B), elimination of low-weighted spots (C) or energy layers (D). The trade-off between dosimetric quality (step I) and treatment time (step II) is controlled during the optimization by option-dependent parameters. PrEfOpt was applied to a clinical patient case, and plans for different trade-offs were calculated. Delivery times were simulated for two virtual facilities with constant and variable proton current, i.e. independent and dependent on the optimized spot weight distributions. Delivery times decreased without major degradation of plan quality; absolute time reductions varied with the applied method and facility type. Minimizing the total spot weight sum (A) reduced times by 28% for a similar plan quality at a constant current (changes of minimum dose in the target  <1%). For a variable proton current, eliminating low-weighted spots (C) led to remarkably faster delivery (16%). The implementation of an efficiency-optimization step into the optimization process can yield reduced delivery times with similar plan qualities. A potential clinical application of PrEfOpt is the generation of multiple plans with different trade

  17. Survey of resident education in intensity-modulated radiation therapy.

    PubMed

    Malik, Renuka; Oh, Julia L; Roeske, John C; Mundt, Arno J

    2005-06-01

    Intensity-modulated radiation therapy (IMRT) has been gaining increasing popularity among practicing physicians in the U.S., but the extent to which radiation oncology residents are taught the principles of this technology and are trained to use IMRT remains unknown. In this paper, we assessed the current level of resident education in IMRT in the United States. Chief residents at all 77 accredited radiation oncology programs were sent a 13-question survey addressing formal didactics and hands-on experience in IMRT. The survey assessed the frequency, subject, and format of IMRT didactics. Questions also addressed the number of IMRT patients and anatomical sites treated, resident involvement in the IMRT process, and the intent of IMRT use. Finally, residents were asked for their opinions on their IMRT education. Sixty-one surveys (79%) were completed. Overall, forty-three respondents (71%) reported receiving formal IMRT didactics, with nearly one-third reporting extensive didactics (> or = 3 lectures/seminars et cetera per year). The most common didactic formats were lectures (95%) and journal clubs (63%), most commonly supervised by physicists (98%). Involvement by physicians and radiobiologists were reported by 63% and 7% of respondents, respectively. Overall, 87% of respondents had hands-on IMRT training, with nearly one-half having treated > 25 patients. The most common sites treated were head and neck (94%) and prostate (81%). Involvement in all aspects of the IMRT process was common, particularly target and tissue delineation (98%) and plan evaluation (93%). Most respondents (79%) with hands-on experience reported receiving formal didactics. However, nearly one-third received no or only minimal formal didactics. The percentage of respondents desiring increased IMRT didactics and hands-on experience were 70% and 47%, respectively. Our results suggest that the great majority of radiation oncology residents in the United States are currently exposed to didactics

  18. Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma

    SciTech Connect

    Yang, Joanna C.; Dharmarajan, Kavita V.; Wexler, Leonard H.; La Quaglia, Michael P.; Happersett, Laura; Wolden, Suzanne L.

    2012-11-01

    Purpose: To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT). Patients and Methods: A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains. Results: With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged {<=}7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions. Conclusions: DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.

  19. Resistant starch is more effective than cholestyramine as a lipid-lowering agent in the rat.

    PubMed

    Younes, H; Levrat, M A; Demigné, C; Rémésy, C

    1995-09-01

    Amylase-resistant starch (RS) represents a substrate for the bacterial flora of the colon, and the question arises as whether RS shares with soluble fibers common mechanisms for their lipid-lowering effects. It is uncertain whether a cholesterol-lowering effect depends basically on an enhanced rate of steroid excretion or whether colonic fermentations also play a role in this effect. In the present study, the effect of RS (25% raw potato starch), of a steroid sequestrant (0.8% cholestyramine), or both were compared on bile acid excretion and lipid metabolism in rats fed semipurified diets. RS diets led to a marked rise in cecal size and the cecal pool of short-chain fatty acids (SCFA), as well as SCFA absorption; cholestyramine did not noticeably affect cecal fermentation. Whereas cholestyramine was particularly effective at enhancing bile acid excretion, RS was more effective in lowering plasma cholesterol (-32%) and triglycerides (-29%). The activity of 3-hydroxy-3-methylglutaryl-CoA reductase was increased fivefold by cholestyramine and twofold by RS. This induction in rats fed RS diets was concomittant to a depressed fatty acid synthase activity. In rats fed the RS diet, there was a lower concentration of cholesterol in all lipoprotein fractions, especially the (d = 1.040-1.080) fraction high-density lipoprotein (HDL1), while those fed cholestyramine had only a significant reduction of HDL1 cholesterol. In contrast to cholestyramine, RS also depressed the concentration of triglycerides in the triglyceride-rich lipoprotein fraction.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. [Study on lipid-lowering traditional Chinese medicines based on pharmacophore technology and patent retrieval].

    PubMed

    Huo, Xiao-qian; He, Yu-su; Qiao, Lian-sheng; Sun, Zhi-yi; Zhang, Yan-ling

    2014-12-01

    The combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple application, but with stronger adverse reactions at the same time. In the treatment of hyperlipidemia, the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactions, and provides a new option for the combined application of drugs. In this article, the pharmacophore technology was used to search chemical components of TCMs, trace their source herbs, and determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classics, to ensure the high safety and efficacy of all selected TCMs, we selected TCMs that are proved to be combined with statins in the World Traditional/Natural Medicine Patent Database, analyzed corresponding drugs in pharmacophore results based on that, and finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically, the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the model, optimize with the Screen Library module, and get the best sub-pharmacophore, which consisted of two hydrogen bond acceptor, three hydrophobic groups and 19 excluded volumes, with the identification effectiveness index value N of 2. 82 and the comprehensive evaluation index CAI value of 1. 84. The model was used to screen the TCMD database, hit 5,235 kinds of chemical components and 1 193 natural animals and plants, and finally determine 62 TCMs. Through patent retrieval, we found 38 TCMs; After comparing with the virtual screening results, we finally got seven TCMs.

  1. Statins as Regulators of Redox State in the Vascular Endothelium: Beyond Lipid Lowering

    PubMed Central

    Margaritis, Marios; Channon, Keith M.

    2014-01-01

    Abstract Significance: Endothelial dysfunction and the imbalance between nitric oxide (NO) and reactive oxygen species production in the vascular endothelium are important early steps in atherogenesis, a major socioeconomic health problem. Statins have well-established roles in primary and secondary prevention of cardiovascular disease (CVD), due to both their lipid-lowering capacity and their pleiotropic properties. It is therefore important to understand the mechanisms by which statins can modify endothelial function and affect atherogenesis. Recent Advances: In the last decade, the concept of statin pleiotropy has been reinforced by a large number of cell culture, animal, and translational studies. Statins have been shown to suppress the activity of pro-oxidant enzymes (such as NADPH oxidase) and pro-inflammatory transcriptional pathways in the endothelium. At the same time, they enhance endothelial NO synthase expression and activity while they also improve its enzymatic coupling. This leads to increased NO bioavailability and improved endothelial function. Critical Issues: Despite significant recent advances, the exact mechanisms of statin pleitropy are still only partially understood. The vast majority of the published literature relies on animal studies, while the actual mechanistic studies in humans are limited. Future Directions: The success of statins as endothelium redox-modifying agents with a direct impact on clinical outcome highlights the importance of the endothelium as a therapeutic target in CVD. Better understanding of the mechanisms that underlie endothelial dysfunction could lead to the design of novel therapeutic strategies that target the vascular endothelium for the prevention and treatment of CVD. Antioxid. Redox Signal. 20, 1198–1215. PMID:24111702

  2. Changes in N400 Topography Following Intensive Speech Language Therapy for Individuals with Aphasia

    ERIC Educational Resources Information Center

    Wilson, K. Ryan; O'Rourke, Heather; Wozniak, Linda A.; Kostopoulos, Ellina; Marchand, Yannick; Newman, Aaron J.

    2012-01-01

    Our goal was to characterize the effects of intensive aphasia therapy on the N400, an electrophysiological index of lexical-semantic processing. Immediately before and after 4 weeks of intensive speech-language therapy, people with aphasia performed a task in which they had to determine whether spoken words were a "match" or a "mismatch" to…

  3. [Modalities of breast cancer irradiation in 2016: Aims and indications of intensity modulated radiation therapy].

    PubMed

    Bourgier, C; Fenoglietto, P; Lemanski, C; Ducteil, A; Charissoux, M; Draghici, R; Azria, D

    2016-10-01

    Irradiation techniques for breast cancer (arctherapy, tomotherapy) are evolving and intensity-modulated radiation therapy is being increasingly considered for the management of these tumours. Here, we propose a review of intensity-modulated radiation therapy planning issues, clinical toxicities and indications for breast cancer.

  4. Changes in N400 Topography Following Intensive Speech Language Therapy for Individuals with Aphasia

    ERIC Educational Resources Information Center

    Wilson, K. Ryan; O'Rourke, Heather; Wozniak, Linda A.; Kostopoulos, Ellina; Marchand, Yannick; Newman, Aaron J.

    2012-01-01

    Our goal was to characterize the effects of intensive aphasia therapy on the N400, an electrophysiological index of lexical-semantic processing. Immediately before and after 4 weeks of intensive speech-language therapy, people with aphasia performed a task in which they had to determine whether spoken words were a "match" or a "mismatch" to…

  5. Blood Lipid Levels, Lipid Lowering Medications, and the Incidence of Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study

    PubMed Central

    Lopez, Faye L.; Agarwal, Sunil K.; MacLehose, Richard F.; Soliman, Elsayed Z.; Sharrett, A. Richey; Huxley, Rachel R.; Konety, Suma; Ballantyne, Christie M.; Alonso, Alvaro

    2012-01-01

    Background Several cardiovascular risk factors have been associated with the risk of atrial fibrillation (AF). Limited and inconsistent evidence exists on the association of blood lipid levels and lipid lowering medication use with AF risk. Methods and Results We analyzed 13,969 participants (25% African-American, 45% men) free of AF at baseline from the Atherosclerosis Risk in Communities (ARIC) study. Fasting HDL cholesterol (HDLc), LDL cholesterol (LDLc), triglycerides, and total cholesterol were measured at baseline (1987–89) and each of three follow-up visits. Incidence of AF was ascertained through 2007. The association of the use of statins and other lipid lowering medications with AF was estimated in 13,044 ARIC participants attending visit 2 (1990–92), adjusting for covariates from the previous visit. During a median follow-up of 18.7 years there were 1433 incident AF cases. Multivariable hazard ratios (HR) and 95% confidence intervals (CI) of AF associated with a one standard deviation increase in lipid levels were: HDLc: 0.97 (0.91–1.04); LDLc: 0.90 (0.85–0.96); total cholesterol: 0.89 (0.84–0.95); and triglycerides: 1.00 (0.96–1.04). Participants taking lipid lowering medications had an adjusted HR (95% CI) of AF of 0.96 (0.82–1.13) compared to those not on medications, while those taking statins had an adjusted HR of 0.91 (0.66–1.25) compared to those taking other lipid lowering mediations. Conclusions Higher levels of LDLc and total cholesterol were associated with a lower incidence of AF. HDLc and triglycerides, however, were not independently associated with AF incidence. No association was found between the use of lipid lowering medications and incident AF. PMID:22227953

  6. Changes over time in risk factors for cardiovascular disease and use of lipid-lowering drugs in HIV-infected individuals and impact on myocardial infarction.

    PubMed

    Sabin, C A; d'Arminio Monforte, A; Friis-Moller, N; Weber, R; El-Sadr, W M; Reiss, P; Kirk, O; Mercie, P; Law, M G; De Wit, S; Pradier, C; Phillips, A N; Lundgren, J D

    2008-04-01

    Because of the known relationship between exposure to combination antiretroviral therapy and cardiovascular disease (CVD), it has become increasingly important to intervene against risk of CVD in human immunodeficiency virus (HIV)-infected patients. We evaluated changes in risk factors for CVD and the use of lipid-lowering therapy in HIV-infected individuals and assessed the impact of any changes on the incidence of myocardial infarction. The Data Collection on Adverse Events of Anti-HIV Drugs Study is a collaboration of 11 cohorts of HIV-infected patients that included follow-up for 33,389 HIV-infected patients from December 1999 through February 2006. The proportion of patients at high risk of CVD increased from 35.3% during 1999-2000 to 41.3% during 2005-2006. Of 28,985 patients, 2801 (9.7%) initiated lipid-lowering therapy; initiation of lipid-lowering therapy was more common for those with abnormal lipid values and those with traditional risk factors for CVD (male sex, older age, higher body mass index [calculated as the weight in kilograms divided by the square of the height in meters], family and personal history of CVD, and diabetes mellitus). After controlling for these, use of lipid-lowering drugs became relatively less common over time. The incidence of myocardial infarction (0.32 cases per 100 person-years [PY]; 95% confidence interval [CI], 0.29-0.35 cases per 100 PY) appeared to remain stable. However, after controlling for changes in risk factors for CVD, the rate decreased over time (relative rate in 2003 [compared with 1999-2000], 0.73 cases per 100 PY [95% CI, 0.50-1.05 cases per 100 PY]; in 2004, 0.64 cases per 100 PY [95% CI, 0.44-0.94 cases per 100 PY]; in 2005-2006, 0.36 cases per 100 PY [95% CI, 0.24-0.56 cases per 100 PY]). Further adjustment for lipid levels attenuated the relative rates towards unity (relative rate in 2003 [compared with 1999-2000], 1.06 cases per 100 PY [95% CI, 0.63-1.77 cases per 100 PY]; in 2004, 1.02 cases per 100 PY

  7. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

    SciTech Connect

    Lee, Katrina Lenards, Nishele; Holson, Janice

    2016-04-01

    The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.

  8. The acute impact of high-dose lipid-lowering treatment on endothelial progenitor cells in patients with coronary artery disease-The REMEDY-EPC early substudy.

    PubMed

    Madonna, Rosalinda; Renna, Francesca Vera; Lanuti, Paola; Perfetti, Matteo; Marchisio, Marco; Briguori, Carlo; Condorelli, Gerolama; Manzoli, Lamberto; De Caterina, Raffaele

    2017-01-01

    Endothelial progenitor cells (EPCs) play a role in vascular repair, while circulating endothelial cells (CECs) are biomarkers of vascular damage and regeneration. Statins may promote EPC/CEC mobilization in the peripheral blood. We evaluated whether pre-procedural exposure to different lipid-lowering drugs (statins±ezetimibe) can acutely increase levels/activity of EPCs/CECs in patients with stable coronary artery disease (CAD). In a planned sub-analysis of the Rosuvastatin For REduction Of Myocardial DamagE During Coronary AngioplastY (REMEDY) trial, 38 patients with stable CAD on chronic low-dose statin therapy were randomized, in a double-blind, placebo-controlled design, into 4 groups before PCI: i. placebo (n = 11); ii. atorvastatin (80 mg+40 mg, n = 9); iii. rosuvastatin (40 mg twice, n = 9); and iv. rosuvastatin (5 mg) and ezetimibe (10 mg) twice, (n = 9). At baseline and 24 h after treatment-before PCI-, patients underwent blinded analyses of EPCs [colony forming units-endothelial cells (CFU-ECs), endothelial colony-forming cells (ECFCs) and tubulization activity] and CECs in peripheral blood. We found no significant treatment effects on parameters investigated such as number of CECs [Median (IQR): i. 0(0), ii. 4.5(27), iii. 1.9(2.3), iv. 1.9(2.3)], CFU-ECs [Median (IQR): i. 27(11), ii. 19(31), iii. 47(36), iv. 30(98)], and ECFCs [Median (IQR): i. 86(84), ii. 7(84), iii. 8/(42.5), iv. 5(2)], as well as tubulization activity [total tubuli (well), Median (IQR): i. 19(7), ii. 5(4), iii. 25(13), iv. 15(24)]. In this study, we found no evidence of acute changes in levels or activity of EPCs and CECs after high-dose lipid-lowering therapy in stable CAD patients.

  9. Volumetric intensity-modulated arc therapy vs conventional intensity-modulated radiation therapy in nasopharyngeal carcinoma: a dosimetric study

    PubMed Central

    White, Peter; Chan, Kit Chi; Cheng, Ka Wai; Chan, Ka Yiu; Chau, Ming Chun

    2013-01-01

    Dosimetric comparisons between RapidArc (RA) and conventional Intensity-Modulated Radiation Therapy (IMRT) techniques for nasopharyngeal carcinoma (NPC) were performed to address differences in dose coverage of the target, sparing of organs-at-risk (OARs), delivery of monitor units (MUs) and time, to assess whether the RA technique was more beneficial for treatment of NPC. Eight NPC patients (Stages I–IV), who had completed RA treatment, were selected for this study. Computed tomography data sets were re-planned using 7-fields fixed beam IMRT. Quantitative measurements of dose-endpoint values on the dose-volume histograms were carried out for evaluation of: (i) dose homogeneity (D5% – D95%); (ii) degree of conformity (CI95%); (iii) tumor control probability (TCP); (iv) doses to OARs; (v) normal tissue complication probability (NTCP); (vi) treatment time; and (vii) MUs. RA plans achieved better dose conformity and TCP in planning target volumes (PTVs). Target dose homogeneity was not as high as for IMRT plans. Doses to tempero-mandibular joints, clavicles, parotid glands and posterior neck, and their NTCPs were significantly lower in RA plans (P < 0.05). Mean doses to the brainstem and spinal cord were slightly lower in IMRT plans. RA plans allowed for a mean reduction in MUs by 78% (P = 0.006), and a four-fold reduction in treatment delivery times, relative to IMRT plans. RA plans showed superior, or comparable, target coverage and dose conformity in PTVs, but at the expense of inferior dose homogeneity. RA plans also achieved significant improvements in dose reduction to OARs and healthy tissue sparing. A significant reduction in treatment delivery time for RA treatment technique was also noted. PMID:23188186

  10. Extrapleural pneumonectomy, photodynamic therapy and intensity modulated radiation therapy for the treatment of malignant pleural mesothelioma.

    PubMed

    Du, Kevin L; Both, Stefan; Friedberg, Joseph S; Rengan, Ramesh; Hahn, Stephen M; Cengel, Keith A

    2010-09-01

    Intensity modulated radiation therapy (IMRT) has recently been proposed for the treatment of malignant pleural mesothelioma (MPM). Here, we describe our experience with a multimodality approach for the treatment of mesothelioma, incorporating extrapleural pneumonectomy, intraoperative photodynamic therapy and postoperative hemithoracic IMRT. From 2004-2007, we treated 11 MPM patients with hemithoracic IMRT, 7 of whom had undergone porfimer sodium-mediated PDT as an intraoperative adjuvant to surgical debulking. The median radiation dose to the planning treatment volume (PTV) ranged from 45.4-54.5 Gy. For the contralateral lung, V20 ranged from 1.4-28.5%, V5 from 42-100% and MLD from 6.8-16.5 Gy. In our series, 1 patient experienced respiratory failure secondary to radiation pneumonitis that did not require mechanical ventilation. Multimodality therapy combining surgery with increased doses of radiation using IMRT, and newer treatment modalities such as PDT , appears safe. Future prospective analysis will be needed to demonstrate efficacy of this approach in the treatment of malignant mesothelioma. Efforts to reduce lung toxicity and improve dose delivery are needed and provide the promise of improved local control and quality of life in a carefully chosen multidisciplinary approach.

  11. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  12. The Long Term Effectiveness of Intensive Stuttering Therapy: A Mixed Methods Study

    ERIC Educational Resources Information Center

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-01-01

    Purpose: The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. Methods: The…

  13. Comparative analysis of 60Co intensity-modulated radiation therapy

    NASA Astrophysics Data System (ADS)

    Fox, Christopher; Romeijn, H. Edwin; Lynch, Bart; Men, Chunhua; Aleman, Dionne M.; Dempsey, James F.

    2008-06-01

    In this study, we perform a scientific comparative analysis of using 60Co beams in intensity-modulated radiation therapy (IMRT). In particular, we evaluate the treatment plan quality obtained with (i) 6 MV, 18 MV and 60Co IMRT; (ii) different numbers of static multileaf collimator (MLC) delivered 60Co beams and (iii) a helical tomotherapy 60Co beam geometry. We employ a convex fluence map optimization (FMO) model, which allows for the comparison of plan quality between different beam energies and configurations for a given case. A total of 25 clinical patient cases that each contain volumetric CT studies, primary and secondary delineated targets, and contoured structures were studied: 5 head-and-neck (H&N), 5 prostate, 5 central nervous system (CNS), 5 breast and 5 lung cases. The DICOM plan data were anonymized and exported to the University of Florida optimized radiation therapy (UFORT) treatment planning system. The FMO problem was solved for each case for 5-71 equidistant beams as well as a helical geometry for H&N, prostate, CNS and lung cases, and for 3-7 equidistant beams in the upper hemisphere for breast cases, all with 6 MV, 18 MV and 60Co dose models. In all cases, 95% of the target volumes received at least the prescribed dose with clinical sparing criteria for critical organs being met for all structures that were not wholly or partially contained within the target volume. Improvements in critical organ sparing were found with an increasing number of equidistant 60Co beams, yet were marginal above 9 beams for H&N, prostate, CNS and lung. Breast cases produced similar plans for 3-7 beams. A helical 60Co beam geometry achieved similar plan quality as static plans with 11 equidistant 60Co beams. Furthermore, 18 MV plans were initially found not to provide the same target coverage as 6 MV and 60Co plans; however, adjusting the trade-offs in the optimization model allowed equivalent target coverage for 18 MV. For plans with comparable target coverage

  14. [Anesthesia and intensive therapy for a patient with mitochondrial myopathy].

    PubMed

    Breucking, E; Mortier, W; Lampert, R; Brandt, L

    1993-10-01

    Since 1983 we have been involved in the diagnostic work-up and emergency treatment of a female patient now 48 years old who has a mitochondrial myopathy resembling Luft's disease. The syndrome was first described in 1959, and in more detail in 1962, by Luft and et al., who reported a picture of hypermetabolism with high temperature, extreme sweating, tachycardia, dyspnoea at rest, polydipsia, polyphagia and irritability but normal thyroid function. In 1971 and 1976 Haydar and Di Mauro presented a second case and proposed treatment with chloramphenicol. Our patient has the third case of the syndrome reported so far: her case was initially published in 1987. CASE REPORT. Since her 17th year of life the patient had suffered from episodes of fever, tachycardia and sweating. At the age of 32 these attacks worsened, leading to unconsciousness and apnoea. The patient then had to be intubated, ventilated and sometimes resuscitated. The diagnosis of MH susceptibility and Luft's disease was made on biochemical grounds after the first muscle biopsy in 1983. Therapy with chloramphenicol failed. Therapy with beta blockers, vitamin C and K or E, coenzyme Q10 and a high-caloric diet was started in 1985. The patient was registered with an emergency service, which flew her to our ICU whenever she had a severe crisis. For milder episodes she was supplied with an oxygen breathing mask at home. Myalgia increased with the episodes starting in 1988, and the patient needed dantrolene infusions and analgesics at home. To facilitate venepuncture a Port-A-Cath system was implanted in 1987, which had to be removed four times due to infection and sepsis. A muscle biopsy was taken in Rotterdam, which revealed differences in mitochondrial function from the biochemical findings recorded in 1983 and not in keeping with Luft's disease. Unfortunately, the patient was not able to undergo further metabolic investigations or therapeutic trials. ANAESTHESIA. The patient received three local and six

  15. Effects of nonlinear ultrasound propagation on high intensity brain therapy.

    PubMed

    Pinton, Gianmarco; Aubry, Jean-Francois; Fink, Mathias; Tanter, Mickael

    2011-03-01

    As an ultrasound wave propagates nonlinearly, energy is transferred to higher frequencies where it is more strongly attenuated. Compared to soft tissue, the skull has strongly heterogeneous material parameters. The authors characterize with experiments and establish a numerical method that can describe the effects of the skull on the nonlinear components of ultrasonic wave propagation for application to high intensity focused ultrasound (HIFU) therapy in the brain. The impact of nonlinear acoustic propagation on heat deposition and thermal dose delivery is quantified and compared to linear assumptions by coupling an acoustic simulation with a heating model for brain tissue. A degassed dessicated human skull was placed in a water tank and insonified at 1 MPa with 7 mm transducer from a custom array designed for HIFU treatment. Two dimensional scans were performed preceding and following propagation through the skull with a calibrated hydrophone. Data from the scan preceding the skull were used as an input to a three dimensional finite difference time domain (FDTD) simulation that calculates the effects of diffraction, density, attenuation with linear dependence on frequency via relaxation mechanisms, and second order nonlinearity. A measured representation of the skull was used to determine the skull's acoustic properties. The validated acoustic model was used to determine the loss due to nonlinear propagation and then coupled to a finite difference simulation of the bioheat equation for two focal configurations at 3 and 7.5 cm from the skull surface. Prior to propagation through the skull, the second harmonic component was 19 dB lower than the fundamental, and the third harmonic component was 37 dB lower. Following the skull, the second harmonic component was 35 dB lower and the third harmonic was 55 dB lower. The simulation is in agreement with the measurements to within 0.5 dB across the considered frequency range and shows good agreement across the two

  16. Nutritional therapy in paediatric intensive care units: a consensus statement of the Section of Paediatric Anaesthesia and Intensive Therapy the Polish Society of Anaesthesiology and Intensive Therapy, Polish Society of Neonatology and Polish Society for.

    PubMed

    Bartkowska-Śniatkowska, Alicja; Zielińska, Marzena; Świder, Magdalena; Bittner, Grażyna; Sarnowska-Wroczyńska, Irena; Witulska, Katarzyna; Migdał, Marek; Piotrowski, Andrzej; Bober-Olesińska, Krystyna; Kęsiak, Marcin; Lauterbach, Ryszard; Gawecka, Agnieszka; Danko, Mikołaj; Popińska, Katarzyna; Romanowska, Hanna; Szlagatys-Sidorkiewicz, Agnieszka; Toporowska-Kowalska, Ewa; Żyła, Aleksandra; Książyk, Janusz

    2015-01-01

    Providing nutritional therapy via the gastrointestinal tract in patients in paediatric intensive care units (PICUs) is an effective method for delivering energy and other nutrients. In the event of contraindications to using this method, it is necessary to commence parenteral nutrition. In the present study, methods for nutritional treatments in critically ill children are presented, depending on the clinical situation.

  17. The psychophysiological effects of music therapy in intensive care units.

    PubMed

    Austin, Donna

    2010-04-01

    This article reviews the evidence for using music therapy with young people who are supported by mechanical ventilation. The author argues that music therapy is essential for developing a holistic approach focusing on the developmental level of a child or young person, as well as being an inexpensive, non-pharmacological, non-invasive therapy, with significant physiological and psychological benefits. She argues that more research is needed in this area to develop a sound evidence base on which guidelines to inform practice could be based.

  18. Impact of machines on plan quality: volumetric modulated arc therapy and intensity modulated radiation therapy.

    PubMed

    Clemente, S; Cozzolino, M; Oliviero, C; Fiorentino, A; Chiumento, C; Fusco, V

    2014-02-01

    To evaluate the impact of different machines on plan quality using both intensity modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) techniques. Eight patients with squamous cell carcinoma of the oropharynx were selected at random. Plans were computed for IMRT and VMAT Smart Arc, using Pinnacle TPS for an Elekta (IMRT-E, VMAT-E) and Varian linac (IMRT-V, VMAT-V). A three-dose level prescription was used to deliver 70, 63 and 58.1 Gy to regions of macroscopic, microscopic high- and low-risk disease, respectively. All doses were given in 35 fractions. Comparisons were performed on dose-volume histogram data, monitor units (MU), and delivery time. VMAT-E plans resulted slightly MU efficient (-24 % p < 0.05) compared to VMAT-V while IMRT-V shortened delivery time (-19 % p < 0.05) compared to IMRT-E. All the delivery techniques resulted in equivalent target coverage in terms of D(98) % and D(2) %. For VMAT technique, a significant improvement of 7 % in homogeneity index (HI) for PTV58.1 was observed for Varian machine. A slight improvement in OARs sparing was observed with Elekta machine both for IMRT and VMAT techniques. Similar plan quality was observed for Elekta and Varian linacs, significant differences were observed in delivery efficiency, as MU number and delivery times, in favor of Elekta and Varian, respectively.

  19. Trends in prescribing and utilization of statins and other lipid lowering drugs across Europe 1997–2003

    PubMed Central

    Walley, T; Folino-Gallo, P; Stephens, P; Van Ganse, E

    2005-01-01

    Aims To describe trends in utilization and prescribing of statins and other lipid lowering drugs across Europe from data in routine administrative databases. Methods Observational study in EU member states and Norway. Comparison of annual utilization data for lipid lowering agents by class and drug from national administrative databases for reimbursement over the period 1997–2003, measured in DDDs per 1000 inhabitants/day. Prescribed daily doses (PDD) of statins obtained from a commercial database (IMS Health) for 2000 and 2003, and used to calculate numbers of ‘patient treatment days’ (PTD) in each country in each year. Analysis of PTD to explain increased utilization of statins. Results Use of lipid lowering agents varied among countries (in 2003, highest in Ireland and Norway, and lowest in Italy), but increased in all countries studied (between 2000 and 2003 by 274%in Ireland and by 56%in France). This increase was entirely due to increases in statin use. Prescribed daily doses of statins increased in all countries for which data was available between 2000 and 2003, but still usually fell below the doses used in the major trials of statins. As a result, the numbers of PTDs increased to a lesser extent than suggested by utilization (e.g. by 192% in Ireland and by 35% in France). One-third of the total rise in utilization was explained by increased PDD, and two-thirds by an increase in numbers of PTDs. Statins dominated the markets in all countries, although fibrates remained strong in France and Belgium (approximately 25% of all lipid lowering agents) and to a lesser extent Germany (10%). Conclusions Use of statins across Europe has increased hugely over the study period. Some of the increase in use is due to higher prescribed daily doses, but two-thirds is due to increases in numbers of patient days of treatment, either due to more patients treated or less likely to better compliance. PMID:16236045

  20. Changing practice with changing research: results of two UK national surveys of intensive insulin therapy in intensive care patients.

    PubMed

    Paddle, J J; Eve, R L; Sharpe, K A

    2011-02-01

    We conducted two telephone surveys of all United Kingdom adult intensive care units in 2007/8 and 2010 to assess practice with regard to intensive insulin therapy for glycaemic control in critically ill patients, and to assess the change in practice following publications in 2008 and 2009 that challenged the evidence for this therapy. Of 243 units that had a written policy for intensive insulin therapy in 2007/8, 232 (96%) still had a policy in 2010. One hundred and six (46%) units had updated their policy in response to new evidence, whereas 126 (54%) stated that it had remained the same. Where intensive care units had changed their policy, we found a significant increase in target limits and a wider target range. Regional variations in practice were also seen. Across seven regions, the percentage of units where the glycaemic control policy had been updated since 2007/8 varied from nil to 78.9%. © 2011 The Authors. Anaesthesia © 2011 The Association of Anaesthetists of Great Britain and Ireland.

  1. Intensive Stuttering Modification Therapy: A Multidimensional Assessment of Treatment Outcomes

    ERIC Educational Resources Information Center

    Blomgren, Michael; Roy, Nelson; Callister, Thomas; Merrill, Ray M.

    2005-01-01

    Nineteen adults who stutter participated in a 3-week intensive stuttering modification treatment program (the Successful Stuttering Management Program [SSMP]). A series of 14 fluency and affective-based measures were assessed before treatment, immediately after treatment, and 6 months after treatment. Measures included stuttering frequency; the…

  2. Effectiveness of Intensive, Group Therapy for Teenagers Who Stutter

    ERIC Educational Resources Information Center

    Fry, Jane; Millard, Sharon; Botterill, Willie

    2014-01-01

    Background: Treatment of adolescents who stutter is an under-researched area that would benefit from greater attention. Aims: To investigate whether an intensive treatment programme for older teenagers who stutter, aged over 16 years of age, is effective in reducing overt and covert aspects of stuttering. Methods & Procedures: A…

  3. Effectiveness of Intensive, Group Therapy for Teenagers Who Stutter

    ERIC Educational Resources Information Center

    Fry, Jane; Millard, Sharon; Botterill, Willie

    2014-01-01

    Background: Treatment of adolescents who stutter is an under-researched area that would benefit from greater attention. Aims: To investigate whether an intensive treatment programme for older teenagers who stutter, aged over 16 years of age, is effective in reducing overt and covert aspects of stuttering. Methods & Procedures: A…

  4. Intensive Stuttering Modification Therapy: A Multidimensional Assessment of Treatment Outcomes

    ERIC Educational Resources Information Center

    Blomgren, Michael; Roy, Nelson; Callister, Thomas; Merrill, Ray M.

    2005-01-01

    Nineteen adults who stutter participated in a 3-week intensive stuttering modification treatment program (the Successful Stuttering Management Program [SSMP]). A series of 14 fluency and affective-based measures were assessed before treatment, immediately after treatment, and 6 months after treatment. Measures included stuttering frequency; the…

  5. Effect of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) on Conduction System Disease.

    PubMed

    Dewland, Thomas A; Soliman, Elsayed Z; Davis, Barry R; Magnani, Jared W; Yamal, Jose-Miguel; Piller, Linda B; Haywood, L Julian; Alonso, Alvaro; Albert, Christine M; Marcus, Gregory M

    2016-08-01

    Cardiac conduction abnormalities are associated with an increased risk for morbidity and mortality, and understanding factors that accelerate or delay conduction system disease could help to identify preventive and therapeutic strategies. Antifibrotic and anti-inflammatory properties of angiotensin-converting enzyme inhibitors and treatment for hyperlipidemia may reduce the risk for incident conduction system disease. To identify the effect of pharmacologic therapy randomization and clinical risk factors on the incidence of conduction system disease. This secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) investigation acquired data from 623 North American centers. A total of 21 004 ambulatory individuals 55 years or older with hypertension and at least 1 other cardiac risk factor were included in the analysis. Participants were randomly assigned to receive amlodipine besylate, lisinopril, or chlorthalidone. Individuals with elevated fasting low-density lipoprotein cholesterol levels were also randomized to pravastatin sodium vs usual care. An electrocardiogram (ECG) was obtained at study enrollment and every 2 years of follow-up. The development of incident first-degree atrioventricular block, left anterior fascicular block, incomplete left bundle branch block (LBBB), LBBB, incomplete right bundle branch block (RBBB), RBBB, or intraventricular conduction delay was assessed by serial ECGs. The 21 004 participants (11 758 men [56.0%]; 9246 women [44.0%]; mean [SD] age, 66.5 [7.3] years) underwent a mean (SD) follow-up of 5.0 (1.2) years. Among the 1114 participants who developed any conduction defect, 389 developed LBBB, 570 developed RBBB, and 155 developed intraventricular conduction delay. Compared with chlorthalidone, randomization to lisinopril was associated with a significant 19% reduction in conduction abnormalities (hazard ratio [HR], 0.81; 95% CI, 0.69-0.95; P = .01). Treatment with

  6. Clinical effects of intensive insulin therapy treating traumatic shock combined with multiple organ dysfunction syndrome.

    PubMed

    Du, Jundong; Liu, Hongming; Liu, Rong; Yao, Yongming; Jiao, Huabo; Zhao, Xiaodong; Yin, Huinan; Li, Zhanliang

    2011-04-01

    The therapeutic effects of intensive insulin therapy in treatment of traumatic shock combined with multiple organ dysfunction syndrome (MODS) were investigated. A total of 114 patients with traumatic shock combined with MODS were randomly divided into two groups: control group (n=56) treated with conventional therapy, and intensive insulin therapy group (n=58) treated with conventional therapy plus continuous insulin pumping to control the blood glucose level at range of 4.4-6.1 mmol/L. White blood cells (WBC) counts, prothrombin time (PT), serum creatinine (SCr), alanine aminotransferase (ALT), serum albumin and PaO(2) were measured before and at the day 1, 3, 5, 7 and 14 after treatment. The incidence of gastrointestinal dysfunction, the incidence of MODS, hospital stay and the mortality were also observed and compared. After intensive insulin therapy, the WBC counts, SCr, ALT and PT were significantly reduced (P<0.05), but the level of serum albumin was significantly increased (P<0.05) at the day 3, 5, 7 and 14. In the meantime, the PaO2 was significantly elevated at the day 3, 5 and 7 (P<0.01) after intensive insulin therapy. The incidence of gastrointestinal dysfunction, the incidence of MODS, the length of hospital stay and the mortality were markedly decreased (P<0.01). The results suggest early treatment with intensive insulin therapy is effective for traumatic shock combined with MODS and can decrease the length of hospital stay and the mortality.

  7. Effects of intensive insulin therapy combined with low molecular weight heparin anticoagulant therapy on severe pancreatitis

    PubMed Central

    DU, JUN-DONG; ZHENG, XI; HUANG, ZHI-QIANG; CAI, SHOU-WANG; TAN, JING-WANG; LI, ZHAN-LIANG; YAO, YONG-MING; JIAO, HUA-BO; YIN, HUI-NAN; ZHU, ZI-MAN

    2014-01-01

    The current study explored the effects of intensive insulin therapy (IIT) combined with low molecular weight heparin (LMWH) anticoagulant therapy on severe acute pancreatitis (SAP). A total of 134 patients with SAP that received treatment between June 2008 and June 2012 were divided randomly into groups A (control; n=33), B (IIT; n=33), C (LMWH; n=34) and D (IIT + LMWH; n=34). Group A were treated routinely. Group B received continuous pumped insulin, as well as the routine treatment, to maintain the blood sugar level between 4.4 and 6.1 mmol/l. Group C received a subcutaneous injection of LMWH every 12 h in addition to the routine treatment. Group D received IIT + LMWH and the routine treatment. The white blood cell count, hemodiastase, serum albumin, arterial partial pressure of oxygen and prothrombin time were recorded prior to treatment and 1, 3, 5, 7 and 14 days after the initiation of treatment. The intestinal function recovery time, incidence rate of multiple organ failure (MOF), length of hospitalization and fatality rates were observed. IIT + LMWH noticeably increased the white blood cell count, hemodiastase level, serum albumin level and the arterial partial pressure of oxygen in the patients with SAP (P<0.05). It markedly shortened the intestinal recovery time and the length of stay and reduced the incidence rate of MOF, the surgery rate and the fatality rate (P<0.05). It did not aggravate the hemorrhagic tendency of SAP (P>0.05). IIT + LMWH had a noticeably improved clinical curative effect on SAP compared with that of the other treatments. PMID:24944612

  8. Lipid-lowering for prevention of coronary heart disease: what policy now?

    PubMed

    Ul Haq, I; Ramsay, L E; Pickin, D M; Yeo, W W; Jackson, P R; Payne, J N

    1996-10-01

    1. Recent outcome trials suggest that lipid-lowering with 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors is justifiable on risk-benefit grounds in subjects with serum cholesterol > 5.5 mmol/l who have coronary heart disease, other forms of atherosclerotic vascular disease, or who are free of vascular disease but have a risk of major coronary events > or = 1.5% per year. Choice of an appropriate treatment policy will require (i) knowledge of the proportion of the population who will need treatment for secondary prevention, and (ii) targeting of treatment for primary prevention at a specified absolute risk of coronary heart disease events. Selection of an appropriate coronary heart disease risk for primary prevention requires consideration of the number needed to be treated to prevent one coronary heart disease event, the proportion of the population requiring treatment, the cost-effectiveness of treatment and the total cost of treatment. 2. In a random stratified sample of subjects aged 35-69 years from the Health Survey for England 1993 we first examined the prevalence of subjects with cardiovascular disease and serum cholesterol > 5.5 mmol/l who may be candidates for secondary prevention. In those free of cardiovascular disease we then examined the prevalence of subjects with serum cholesterol > 5.5 mmol/l who had three different levels of coronary heart disease risk: coronary heart disease event rates of 4.5% per year, 3.0% per year and 1.5% per year. These subjects may be candidates for primary prevention depending on the treatment policy selected. 3. For secondary prevention, 4.8% (95% confidence interval 4.3-5.3) of the U.K. population aged 35-69 years might be candidates for 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor treatment, comprising 2.4% (2.0 to 2.7) with a history of myocardial infarction, 1.9% (1.6 to 2.2) with angina and 0.5% (0.3-0.7) with a history of stroke--all with total cholesterol > 5.5 mmol/l. The prevalence of

  9. [Intensive insulin therapy in type 2 diabetes mellitus].

    PubMed

    Jermendy, György

    2012-09-23

    In the last couple of years, the intensive conservative insulin treatment (basal-bolus regime) became more and more popular even in patients with type 2 diabetes. Using this insulin treatment, continuous patient education, co-operation between the medical team (diabetologist, dietician and diabetes-nurses) and the patient as well as the availability of modern insulins, pens and glucometers are of great importance. Clearly, the basal-bolus treatment with human insulin has advantages over the conservative (conventional) treatment with twice daily premix insulins. Moreover, the basal-bolus treatment with insulin-analogues proved to be superior in some aspects as compared to human insulins. The intensive insulin treatment (basal-bolus regime with insulin-analogues) approaches the optimal insulin substitution and, with its use the adequate correction of each element of the glucose triad (fasting blood glucose, postprandial blood glucose, HbA1c) should be considered feasible even in patients with type 2 diabetes.

  10. Description of an Intensive Dialectical Behavior Therapy Program for Multidiagnostic Clients with Eating Disorders

    ERIC Educational Resources Information Center

    Federici, Anita; Wisniewski, Lucene; Ben-Porath, Denise

    2012-01-01

    The authors describe an intensive outpatient dialectical behavior therapy (DBT) program for multidiagnostic clients with eating disorders who had not responded adequately to standard, empirically supported treatments for eating disorders. The program integrates DBT with empirically supported cognitive behavior therapy approaches that are well…

  11. Physical Therapy Observation and Assessment in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Campbell, Suzann K.

    2013-01-01

    This article presents the elements of the Observation and Assessment section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy assessments presented in this path are evidence-based and the suggested timing of these assessments is primarily based on practice knowledge from expert…

  12. Physical Therapy Observation and Assessment in the Neonatal Intensive Care Unit

    ERIC Educational Resources Information Center

    Byrne, Eilish; Campbell, Suzann K.

    2013-01-01

    This article presents the elements of the Observation and Assessment section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy assessments presented in this path are evidence-based and the suggested timing of these assessments is primarily based on practice knowledge from expert…

  13. Description of an Intensive Dialectical Behavior Therapy Program for Multidiagnostic Clients with Eating Disorders

    ERIC Educational Resources Information Center

    Federici, Anita; Wisniewski, Lucene; Ben-Porath, Denise

    2012-01-01

    The authors describe an intensive outpatient dialectical behavior therapy (DBT) program for multidiagnostic clients with eating disorders who had not responded adequately to standard, empirically supported treatments for eating disorders. The program integrates DBT with empirically supported cognitive behavior therapy approaches that are well…

  14. Intensive diabetes therapy and glomerular filtration rate in type 1 diabetes.

    PubMed

    de Boer, Ian H; Sun, Wanjie; Cleary, Patricia A; Lachin, John M; Molitch, Mark E; Steffes, Michael W; Zinman, Bernard

    2011-12-22

    An impaired glomerular filtration rate (GFR) leads to end-stage renal disease and increases the risks of cardiovascular disease and death. Persons with type 1 diabetes are at high risk for kidney disease, but there are no interventions that have been proved to prevent impairment of the GFR in this population. In the Diabetes Control and Complications Trial (DCCT), 1441 persons with type 1 diabetes were randomly assigned to 6.5 years of intensive diabetes therapy aimed at achieving near-normal glucose concentrations or to conventional diabetes therapy aimed at preventing hyperglycemic symptoms. Subsequently, 1375 participants were followed in the observational Epidemiology of Diabetes Interventions and Complications (EDIC) study. Serum creatinine levels were measured annually throughout the course of the two studies. The GFR was estimated with the use of the Chronic Kidney Disease Epidemiology Collaboration formula. We analyzed data from the two studies to determine the long-term effects of intensive diabetes therapy on the risk of impairment of the GFR, which was defined as an incident estimated GFR of less than 60 ml per minute per 1.73 m(2) of body-surface area at two consecutive study visits. Over a median follow-up period of 22 years in the combined studies, impairment of the GFR developed in 24 participants assigned to intensive therapy and in 46 assigned to conventional therapy (risk reduction with intensive therapy, 50%; 95% confidence interval, 18 to 69; P=0.006). Among these participants, end-stage renal disease developed in 8 participants in the intensive-therapy group and in 16 in the conventional-therapy group. As compared with conventional therapy, intensive therapy was associated with a reduction in the mean estimated GFR of 1.7 ml per minute per 1.73 m(2) during the DCCT study but during the EDIC study was associated with a slower rate of reduction in the GFR and an increase in the mean estimated GFR of 2.5 ml per minute per 1.73 m(2) (P<0.001 for

  15. Delivery confirmation of bolus electron conformal therapy combined with intensity modulated x-ray therapy

    SciTech Connect

    Kavanaugh, James A.; Hogstrom, Kenneth R.; Fontenot, Jonas P.; Henkelmann, Gregory; Chu, Connel; Carver, Robert A.

    2013-02-15

    Purpose: The purpose of this study was to demonstrate that a bolus electron conformal therapy (ECT) dose plan and a mixed beam plan, composed of an intensity modulated x-ray therapy (IMXT) dose plan optimized on top of the bolus ECT plan, can be accurately delivered. Methods: Calculated dose distributions were compared with measured dose distributions for parotid and chest wall (CW) bolus ECT and mixed beam plans, each simulated in a cylindrical polystyrene phantom that allowed film dose measurements. Bolus ECT plans were created for both parotid and CW PTVs (planning target volumes) using 20 and 16 MeV beams, respectively, whose 90% dose surface conformed to the PTV. Mixed beam plans consisted of an IMXT dose plan optimized on top of the bolus ECT dose plan. The bolus ECT, IMXT, and mixed beam dose distributions were measured using radiographic films in five transverse and one sagittal planes for a total of 36 measurement conditions. Corrections for film dose response, effects of edge-on photon irradiation, and effects of irregular phantom optical properties on the Cerenkov component of the film signal resulted in high precision measurements. Data set consistency was verified by agreement of depth dose at the intersections of the sagittal plane with the five measured transverse planes. For these same depth doses, results for the mixed beam plan agreed with the sum of the individual depth doses for the bolus ECT and IMXT plans. The six mean measured planar dose distributions were compared with those calculated by the treatment planning system for all modalities. Dose agreement was assessed using the 4% dose difference and 0.2 cm distance to agreement. Results: For the combined high-dose region and low-dose region, pass rates for the parotid and CW plans were 98.7% and 96.2%, respectively, for the bolus ECT plans and 97.9% and 97.4%, respectively, for the mixed beam plans. For the high-dose gradient region, pass rates for the parotid and CW plans were 93.1% and 94

  16. The effects of high intensity laser therapy on pain and function in patients with knee osteoarthritis.

    PubMed

    Kim, Gook-Joo; Choi, Jioun; Lee, Sangyong; Jeon, Chunbae; Lee, Kwansub

    2016-11-01

    [Purpose] The purpose of this study was to examine the effects of high intensity laser therapy (HILT) on pain and function in patients with knee osteoarthritis. [Subjects and Methods] In this study, an experiment was conducted on 20 subjects who were divided into the control group (n=10), which would receive conservative physical therapy (CPT), and the experimental group (n=10), which would receive effects of high intensity laser therapy after conservative physical therapy. All patients received their respective therapies three times each week over a four-week period. In terms of the intensity of the high intensity laser therapy, it was applied to each patient in the tibia and femoral epicondyle for five minutes while the patient's knee joint was bent at around 30° and the separation distance between the handpiece and the skin was maintained at around 1 cm. The visual analogue scale was used to measure pain, and the Korean Western Ontario and McMaster Universities Osteoarthritis Index was used for functional evaluations. [Results] The comparison of differences in the measurements taken before and after the experiment within each group showed a statistically significant decline in both the VAS and the K-WOMAC. The comparison of the two groups showed that the high intensity laser therapy group had statistically significant lower scores in both the visual analogue scale and the Korean Western Ontario and McMaster Universities Osteoarthritis Index than the conservative physical therapy group. [Conclusion] High intensity laser therapy is considered an effective non-surgical intervention for reducing pain in patients with knee osteoarthritis and helping them to perform daily activities.

  17. The effects of high intensity laser therapy on pain and function in patients with knee osteoarthritis

    PubMed Central

    Kim, Gook-Joo; Choi, Jioun; Lee, Sangyong; Jeon, Chunbae; Lee, Kwansub

    2016-01-01

    [Purpose] The purpose of this study was to examine the effects of high intensity laser therapy (HILT) on pain and function in patients with knee osteoarthritis. [Subjects and Methods] In this study, an experiment was conducted on 20 subjects who were divided into the control group (n=10), which would receive conservative physical therapy (CPT), and the experimental group (n=10), which would receive effects of high intensity laser therapy after conservative physical therapy. All patients received their respective therapies three times each week over a four-week period. In terms of the intensity of the high intensity laser therapy, it was applied to each patient in the tibia and femoral epicondyle for five minutes while the patient’s knee joint was bent at around 30° and the separation distance between the handpiece and the skin was maintained at around 1 cm. The visual analogue scale was used to measure pain, and the Korean Western Ontario and McMaster Universities Osteoarthritis Index was used for functional evaluations. [Results] The comparison of differences in the measurements taken before and after the experiment within each group showed a statistically significant decline in both the VAS and the K-WOMAC. The comparison of the two groups showed that the high intensity laser therapy group had statistically significant lower scores in both the visual analogue scale and the Korean Western Ontario and McMaster Universities Osteoarthritis Index than the conservative physical therapy group. [Conclusion] High intensity laser therapy is considered an effective non-surgical intervention for reducing pain in patients with knee osteoarthritis and helping them to perform daily activities. PMID:27942148

  18. Intensive insulin therapy in severely burned pediatric patients: a prospective randomized trial.

    PubMed

    Jeschke, Marc G; Kulp, Gabriela A; Kraft, Robert; Finnerty, Celeste C; Mlcak, Ron; Lee, Jong O; Herndon, David N

    2010-08-01

    Hyperglycemia and insulin resistance have been shown to increase morbidity and mortality in severely burned patients, and glycemic control appears essential to improve clinical outcomes. However, to date no prospective randomized study exists that determines whether intensive insulin therapy is associated with improved post-burn morbidity and mortality. To determine whether intensive insulin therapy is associated with improved post-burn morbidity. A total of 239 severely burned pediatric patients with burns over greater than 30% of their total body surface area were randomized (block randomization 1:3) to intensive insulin treatment (n = 60) or control (n = 179). Demographics, clinical outcomes, sepsis, glucose metabolism, organ function, and inflammatory, acute-phase, and hypermetabolic responses were determined. Demographics were similar in both groups. Intensive insulin treatment significantly decreased the incidence of infections and sepsis compared with controls (P < 0.05). Furthermore, intensive insulin therapy improved organ function as indicated by improved serum markers, DENVER2 scores, and ultrasound (P < 0.05). Intensive insulin therapy alleviated post-burn insulin resistance and the vast catabolic response of the body (P < 0.05). Intensive insulin treatment dampened inflammatory and acute-phase responses by deceasing IL-6 and acute-phase proteins compared with controls (P < 0.05). Mortality was 4% in the intensive insulin therapy group and 11% in the control group (P = 0.14). In this prospective randomized clinical trial, we showed that intensive insulin therapy improves post-burn morbidity. Clinical trial registered with www.clinicaltrials.gov (NCT00673309).

  19. Application of Histogram Analysis in Radiation Therapy (HART) in Intensity Modulation Radiation Therapy (IMRT) Treatments

    NASA Astrophysics Data System (ADS)

    Pyakuryal, Anil

    2009-03-01

    A carcinoma is a malignant cancer that emerges from epithelial cells in structures through out the body.It invades the critical organs, could metastasize or spread to lymph nodes.IMRT is an advanced mode of radiation therapy treatment for cancer. It delivers more conformal doses to malignant tumors sparing the critical organs by modulating the intensity of radiation beam.An automated software, HART (S. Jang et al.,2008,Med Phys 35,p.2812) was used for efficient analysis of dose volume histograms (DVH) for multiple targets and critical organs in four IMRT treatment plans for each patient. IMRT data for ten head and neck cancer patients were exported as AAPM/RTOG format files from a commercial treatment planning system at Northwestern Memorial Hospital (NMH).HART extracted DVH statistics were used to evaluate plan indices and to analyze dose tolerance of critical structures at prescription dose (PD) for each patient. Mean plan indices (n=10) were found to be in good agreement with published results for Linac based plans. The least irradiated volume at tolerance dose (TD50) was observed for brainstem and the highest volume for larynx in SIB treatment techniques. Thus HART, an open source platform, has extensive clinical implications in IMRT treatments.

  20. [Significance of measuring family satisfaction in the intensive therapy unit].

    PubMed

    Suchorzewska, Janina; Basińska, Krystyna

    2011-01-01

    Recently, numerous studies have been devoted to the issues of satisfaction of ITU patients and their families. Good relationships between the medical personnel and family members are essential for interpersonal communication built by both parties. The knowledge of rules ensuring proper relations with patients and their families is an important element of the medical staff education. To date, neither the medical curriculum nor additional training have focused on this issue. Good communication between the patients` families and physicians, thus the feeling of safety and satisfaction with the intensive care provided, should be based on controlled paternalism, provision of reliable information, confidence moulded, by mutual understanding and respect, elimination of impulsive reactions.

  1. Constraint-induced aphasia therapy versus intensive semantic treatment in fluent aphasia.

    PubMed

    Wilssens, Ineke; Vandenborre, Dorien; van Dun, Kim; Verhoeven, Jo; Visch-Brink, Evy; Mariën, Peter

    2015-05-01

    The authors compared the effectiveness of 2 intensive therapy methods: Constraint-Induced Aphasia Therapy (CIAT; Pulvermüller et al., 2001) and semantic therapy (BOX; Visch-Brink & Bajema, 2001). Nine patients with chronic fluent aphasia participated in a therapy program to establish behavioral treatment outcomes. Participants were randomly assigned to one of two groups (CIAT or BOX). Intensive therapy significantly improved verbal communication. However, BOX treatment showed a more pronounced improvement on two communication-namely, a standardized assessment for verbal communication, the Amsterdam Nijmegen Everyday Language Test (Blomert, Koster, & Kean, 1995), and a subjective rating scale, the Communicative Effectiveness Index (Lomas et al., 1989). All participants significantly improved on one (or more) subtests of the Aachen Aphasia Test (Graetz, de Bleser, & Willmes, 1992), an impairment-focused assessment. There was a treatment-specific effect. BOX treatment had a significant effect on language comprehension and semantics, whereas CIAT treatment affected language production and phonology. The findings indicate that in patients with fluent aphasia, (a) intensive treatment has a significant effect on language and verbal communication, (b) intensive therapy results in selective treatment effects, and (c) an intensive semantic treatment shows a more striking mean improvement on verbal communication in comparison with communication-based CIAT treatment.

  2. Strategies for quality assurance of intensity modulated radiation therapy

    NASA Astrophysics Data System (ADS)

    Benedek, Hunor; Isacsson, Ulf; Olevik-Dunder, Maria; Westermark, Mathias; Hållström, Per; Olofsson, Jörgen; Gustafsson, Magnus

    2015-01-01

    In late 2011 The Swedish Society of Radiation Physics formed a working group to concentrate on the Quality Assurance of modern radiation therapy techniques. The given task was to identify and summarise the different QA strategies in Sweden and also the international recommendations. This was used to formulate recommendations for practical guidelines within Sweden. In this paper a brief summery of the group's work is presented. All the Swedish radiation therapy centres do a pre treatment verification measurement as QA for every new IMRT and VMAT plan. Physicists do it and they believe it to be time consuming. A general standpoint from all the centres was that new guidelines and legislation is needed to allow QA that does not require a measurement. Based on various international publications and recommendations the working group has presented two strategies, one where all new plans are checked through measurement and one where no measurement is needed. The measurement- based strategy is basically the same as the one used today with an extended machine QA part. The other presented strategy is process oriented where all the different parts of the treatment chain are checked separately. The final report can be found in Swedish on http://www.radiofysik.org.

  3. Motor physical therapy in hospitalized patients in an intensive care unit: a systematic review.

    PubMed

    Pinheiro, Alessandra Rigo; Christofoletti, Gustavo

    2012-06-01

    To analyze the outcomes achieved by motor physical therapy in critically ill patients admitted to intensive care units. A systematic literature review was performed, and clinical trials published between 2002 and 2011 were included in the study. The search involved the LILACS, SciELO, MedLine, EMBASE and Cochrane databases, using the keywords "intensive care unit", "physiotherapy", "physical therapy", "mobility", "mobilization" and "randomized controlled trials." Two researchers screened the articles independently and included works that addressed the effect of physical therapy on critically ill patients. From an initial analysis of 67 potentially relevant articles, only 8 met the selection criteria and addressed the outcomes of electrostimulation, cycle ergometry and kinesiotherapy techniques. The sample sizes ranged from 8 to 101 subjects, with mean ages between 52 and 79 years. All patients were undergoing invasive mechanical ventilation. Among the analyzed articles, 6 reported significant benefits of motor physical therapy, such as improvement in peripheral muscle strength, respiratory capacity and functionality, in critically ill patients. With this systematic review, it is possible to conclude that motor physical therapy is a feasible and safe therapy for critically ill patients and can minimize the deleterious effects of prolonged immobilization. Approaches involving electrostimulation, cycle ergometry and kinesiotherapy showed positive responses in patients under intensive care. Available evidence regarding the impact of motor physical therapy on length of stay in intensive care units and on mortality is still scarce, and further study in this area is warranted.

  4. [Complications of resuscitation and intensive therapy in infants (proceedings)].

    PubMed

    Ivanovskaia, T E; Kogoĭ, T F; Pokrovskaia, L Ia; Larina, T M

    1980-01-01

    Most frequent complications of infusion therapy in children include thrombosis and thrombophlebitis of the umbilical and subclavian veins. In the perinatal period thrombophlebitis of the umbilical vein is due to exogenous infection and becomes the source of umbilical sepsis. Thrombophlebitis of the subclavian vein in nurslings results more frequently from endogenous infection. Because of morpho-functional immaturity in infancy, hyperhydration of tissues is extreme, with vacuolar dystrophy of cells up to their necrosis, particularly in the liver and kidneys. Artificial pulmonary ventilation (APV), particularly in premature newborns, is frequently accompanied by breaks of alveolar septae, development of bullous and interstitial emphysema, pneumothorax. In deeply premature infants APV may be ineffective because of immaturity of the lung tissue.

  5. [Solcoseryl in intensive therapy in severe craniocerebral trauma].

    PubMed

    Marusanov, V E; Miroshnichenko, A G; Nikolau, S A; Petrova, N V; Bichun, A B

    2000-01-01

    The state of processes of lipid peroxidation and antioxidant defense was studied in patients with severe isolated craniocerebral closed injury. It was found that starting from the first days in the hospital the patients demonstrated marked alterations in the thiol-disulfide and ascorbate metabolism, activation of lipid peroxidation processes and lower antioxidant defense. The use of Solcoseryl as a component of the antioxidant therapy in treatment of the above mentioned category of patients resulted in considerably better indices of the thiol-disulfide metabolism. The isolated use of Solcoseryl failed to influence the ascorbate metabolism and lipid peroxidation. Solcoseryl used in combination with the ascorbic acid led to normalization of the thiol-disulfide and ascorbade metabolism without influencing the lipid peroxidation processes. Combined use of Solcoseryl and ascorbic acid promoted normalization of the neurological status and stabilization of the arterial pressure level.

  6. Intensive insulin therapy to maintain normoglycemia after cardiac surgery.

    PubMed

    Van den Berghe, G

    2011-01-01

    Drugs used in the perioperative period could have an effect on survival as recently pointed out by an international consensus conference on the reduction in mortality in cardiac anesthesia and intensive care. Insulin infusion to achieve a strict glycemic control is the best example of how an ancillary (i.e. non-surgical) drug/technique/strategy might influence survival rates in patients undergoing cardiac surgery. The author of this "expert opinion" presents her insights into the use of insulin in this setting and suggest that based on available evidence based medicine, insulin infusion, titrated to "normoglycemia" is a complex intervention, that not only requires the simple administration of a "drug", the hormone insulin, but also needs tools and skills to accurately measure and control blood glucose to achieve normoglycemia while avoiding hypoglycemia and large glucose fluctuations.

  7. Optimization in Radiation Therapy: Applications in Brachytherapy and Intensity Modulated Radiation Therapy

    NASA Astrophysics Data System (ADS)

    McGeachy, Philip David

    Over 50% of cancer patients require radiation therapy (RT). RT is an optimization problem requiring maximization of the radiation damage to the tumor while minimizing the harm to the healthy tissues. This dissertation focuses on two main RT optimization problems: 1) brachytherapy and 2) intensity modulated radiation therapy (IMRT). The brachytherapy research involved solving a non-convex optimization problem by creating an open-source genetic algorithm optimizer to determine the optimal radioactive seed distribution for a given set of patient volumes and constraints, both dosimetric- and implant-based. The optimizer was tested for a set of 45 prostate brachytherapy patients. While all solutions met the clinical standards, they also benchmarked favorably with those generated by a standard commercial solver. Compared to its compatriot, the salient features of the generated solutions were: slightly reduced prostate coverage, lower dose to the urethra and rectum, and a smaller number of needles required for an implant. Historically, IMRT requires modulation of fluence while keeping the photon beam energy fixed. The IMRT-related investigation in this thesis aimed at broadening the solution space by varying photon energy. The problem therefore involved simultaneous optimization of photon beamlet energy and fluence, denoted by XMRT. Formulating the problem as convex, linear programming was applied to obtain solutions for optimal energy-dependent fluences, while achieving all clinical objectives and constraints imposed. Dosimetric advantages of XMRT over single-energy IMRT in the improved sparing of organs at risk (OARs) was demonstrated in simplified phantom studies. The XMRT algorithm was improved to include clinical dose-volume constraints and clinical studies for prostate and head and neck cancer patients were investigated. Compared to IMRT, XMRT provided improved dosimetric benefit in the prostate case, particularly within intermediate- to low-dose regions (≤ 40 Gy

  8. Dosimetric comparison of volumetric modulated arc therapy and intensity-modulated radiation therapy for pancreatic malignancies

    SciTech Connect

    Ali, Arif N.; Dhabaan, Anees H.; Jarrio, Christie S.; Siddiqi, Arsalan K.; Landry, Jerome C.

    2012-10-01

    Volumetric-modulated arc therapy (VMAT) has been previously evaluated for several tumor sites and has been shown to provide significant dosimetric and delivery benefits when compared with intensity-modulated radiation therapy (IMRT). To date, there have been no published full reports on the benefits of VMAT use in pancreatic patients compared with IMRT. Ten patients with pancreatic malignancies treated with either IMRT or VMAT were retrospectively identified. Both a double-arc VMAT and a 7-field IMRT plan were generated for each of the 10 patients using the same defined tumor volumes, organs at risk (OAR) volumes, dose, fractionation, and optimization constraints. The planning tumor volume (PTV) maximum dose (55.8 Gy vs. 54.4 Gy), PTV mean dose (53.9 Gy vs. 52.1 Gy), and conformality index (1.11 vs. 0.99) were statistically similar between the IMRT and VMAT plans, respectively. The VMAT plans had a statistically significant reduction in monitor units compared with the IMRT plans (1109 vs. 498, p < 0.001). In addition, the doses to the liver, small bowel, and spinal cord were comparable between the IMRT and VMAT plans. However, the VMAT plans demonstrated a statistically significant reduction in the mean left kidney V{sub 25} (9.4 Gy vs. 2.3 Gy, p = 0.018), mean right kidney V{sub 15} (53.4 Gy vs. 45.9 Gy, p = 0.035), V{sub 20} (32.2 Gy vs. 25.5 Gy, p = 0.016), and V{sub 25} (21.7 Gy vs. 14.9 Gy, p = 0.001). VMAT was investigated in patients with pancreatic malignancies and compared with the current standard of IMRT. VMAT was found to have similar or improved dosimetric parameters for all endpoints considered. Specifically, VMAT provided reduced monitor units and improved bilateral kidney normal tissue dose. The clinical relevance of these benefits in the context of pancreatic cancer patients, however, is currently unclear and requires further investigation.

  9. Cell-stimulation therapy of lateral epicondylitis with frequency-modulated low-intensity electric current.

    PubMed

    Aliyev, R M; Geiger, G

    2012-03-01

    In addition to the routine therapy, the patients with lateral epicondylitis included into experimental group were subjected to a 12-week cell-stimulation therapy with low-intensity frequency-modulated electric current. The control group received the same routine therapy and sham stimulation (the therapeutic apparatus was not energized). The efficiency of this microcurrent therapy was estimated by comparing medical indices before therapy and at the end of a 12-week therapeutic course using a 10-point pain severity numeric rating scale (NRS) and Roles-Maudsley pain score. The study revealed high therapeutic efficiency of cell-stimulation with low-intensity electric current resulting probably from up-regulation of intracellular transmitters, interleukins, and prostaglandins playing the key role in the regulation of inflammation.

  10. Three-Phase Adaptive Radiation Therapy for Patients With Nasopharyngeal Carcinoma Undergoing Intensity-Modulated Radiation Therapy: Dosimetric Analysis.

    PubMed

    Deng, Shan; Liu, Xu; Lu, Heming; Huang, Huixian; Shu, Liuyang; Jiang, Hailan; Cheng, Jinjian; Peng, Luxing; Pang, Qiang; Gu, Junzhao; Qin, Jian; Lu, Zhiping; Mo, Ying; Wu, Danling; Wei, Yinglin

    2017-01-01

    Patients with nasopharyngeal carcinoma undergoing intensity-modulated radiation therapy may experience significant anatomic changes throughout the entire treatment course, and adaptive radiation therapy may be necessary to maintain optimal dose delivered both to the targets and to the critical structures. The timing of adaptive radiation therapy, however, is largely unknown. This study was to evaluate the dosimetric benefits of a 3-phase adaptive radiation therapy technique for nasopharyngeal carcinoma. Twenty patients with nasopharyngeal carcinoma treated with intensity-modulated radiation therapy were recruited prospectively. After fractions 5 and 15, each patient had repeat computed tomography scans, and adaptive replans with recontouring the targets and organs at risk on the new computed tomography images were generated and used for subsequent treatment (replan 1 and replan 2). Two hybrid intensity-modulated radiation therapy plans (plan 1 and plan 2) were generated by superimposing the initial plan (plan 0) to each repeated new computed tomography image, reflecting the actual dose delivered to the targets and organs at risk if no changes were made to the original plan. Dosimetric comparisons were made between the adaptive replans (adaptive radiation therapy plans: plan 0 + replan 1 + replan 2) and their corresponding nonadaptive radiation therapy plans (plan 0 + plan 1 + plan 2). Comparing with the nonadaptive radiation therapy plans, the adaptive radiation therapy plans resulted in a significant improvement in conformity index for planning target volumes for primary disease, involved lymph node, high-risk clinical target volume, and low-risk clinical target volume (PTVnx, PTVnd, PTV1, and PTV2, respectively). Median V95 for PTVnx; D95, D99, V100, V95, and V93 for PTVnd; D99 and V100 for PTV1; and D95, D99, V100, V95, and V93 for PTV2 were increased significantly. There were significant dose-volume reductions, including maximum doses to the brainstem and

  11. Pharmacoeconomics of lipid-lowering agents for primary and secondary prevention of coronary artery disease.

    PubMed

    Hay, J W; Yu, W M; Ashraf, T

    1999-01-01

    Cardiovascular disease is the leading cause of death and the leading source of healthcare expenditure in the US and most other industrialised countries. Cholesterol lowering by pharmacological means prevents atherosclerotic plaque progression and has been shown to reduce both fatal and nonfatal coronary events in patients with or without coronary artery disease (CAD). Because of their excellent efficacy and safety profiles, the introduction of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors (also known an 'statins') in 1987 raised hopes for demonstrating the survival benefit of cholesterol reduction. In the past decade, several large-scale placebo-controlled trials with statin therapy have revisited the relationship between cholesterol reduction, cardiovascular disease and mortality. The West of Scotland Coronary Prevention Study (WOSCOPS) [pravastatin] and the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS) [lovastatin] have shown significant cardiovascular disease reduction in primary prevention trials of patients with elevated and normal cholesterol levels, respectively. The Scandinavian Simvastatin Survival Study (4S), the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study and the Cholesterol and Recurrent Events (CARE) trial [pravastatin] have shown significant cardiovascular disease reduction in patients with a previous history of CAD with high, moderate and normal cholesterol levels, respectively. Three of these studies (4S, WOSCOPS and LIPID) have shown significant reduction in all-cause mortality, while all the statin secondary prevention trials (4S, CARE and LIPID) have demonstrated significant reduction in cerebrovascular disease/ Earlier cholesterol reduction cost-effectiveness studies with nonstatin treatments (bile acid resins, fibrates, niacin and diet) suggested that only patients at extremely high risk could be treated with lipid therapy in a cost-effective manner. More

  12. Rosuvastatin reduced deep vein thrombosis in ApoE gene deleted mice with hyperlipidemia through non-lipid lowering effects

    PubMed Central

    Patterson, K.A.; Zhang, X.; Wrobleski, S.K.; Hawley, A.E.; Lawrence, D. A.; Wakefield, T.W.; Myers, D.D.; Diaz, J.A.

    2013-01-01

    Introduction Statins, particularly rosuvastatin, have recently become relevant in the setting of venous thrombosis. The objective of this study was to study the non-lipid lowering effects of rosuvastatin in venous thrombosis in mice with hyperlipidemia. Materials and Methods An inferior vena cava ligation model of venous thrombosis in mice was utilized. Saline or 5mg/kg of rosuvastatin was administered by gavage 48hs previous thrombosis. Blood, the inferior vena cava, thrombus, and liver were harvested 3, 6 hours, and 2 days post-thrombosis. Thrombus weight, inflammatory markers, and plasminogen activator inhibitor-1 expression and plasma levels were measured and neutrophil migration to the IVC was assessed. Results Rosuvastatin significantly decreased thrombus weight, plasminogen activator inhibitor-1 expression and plasma levels, expression of molecules related to the interleukin-6 pathway, and neutrophil migration into the vein wall. Conclusions This work supports the beneficial effects of rosuvastatin on venous thrombosis in mice with hyperlipidemia due to its non-lipid lowering effects. PMID:23276528

  13. Physical therapy in critically ill adult patients: recommendations from the Brazilian Association of Intensive Care Medicine Department of Physical Therapy.

    PubMed

    França, Eduardo Ériko Tenório de; Ferrari, Francimar; Fernandes, Patrícia; Cavalcanti, Renata; Duarte, Antonio; Martinez, Bruno Prata; Aquim, Esperidião Elias; Damasceno, Marta Cristina Paulete

    2012-03-01

    Complications from immobility in intensive care unit patients contribute to functional decline, increased healthcare costs, reduced quality of life and higher post-discharge mortality. Physical therapy focuses on promoting recovery and preserving function, and it may minimize the impact of these complications. A group of Brazilian Association of Intensive Care Medicine physical therapy experts developed this document that contains minimal physical therapy recommendations appropriate to the Brazilian real-world clinical situation. Prevention and treatment of atelectasis, procedures related to the removal of secretions and treatment of conditions related to physical deconditioning and functional decline are discussed. Equally important is the consideration that prescribing and executing activities, mobilizations and exercises are roles of the physical therapist, whose diagnosis should precede any intervention.

  14. Bioactive vegetable proteins and peptides in lipid-lowering; nutraceutical potential.

    PubMed

    Ruiz Ruiz, Jorge Carlos; Betancur Ancona, David Abram; Segura Campos, Maira Rubi

    2014-04-01

    As the last century saw a decline in the burden of nutritional deficiency and infectious disease, the global burden of chronic disease, cardiovascular disease (CVD) in particular, is increasing. CVD is the leading cause of death in the developed countries. Significant research efforts on the prevention and treatment of this disease have identified elevated plasma cholesterol as a primary risk factor for CVD. Although CVD progresses with hypercholesterolemia, it seems possibility to delay and prevent its development through improvement of diet. Recent findings demonstrate that protein concentrates, protein hydrolysates, and peptides derived from vegetables may promote a significant decrease in blood cholesterol concentration. This reduction in cholesterol and lipid levels by protein, protein hydrolysates, and peptides can be the result of dietary changes, reduced cholesterol biosynthesis, changes in bile acid synthesis, and reduced absorption of lipid cholesterol and bile acid. Combination drug/diet therapies may reduce the number of drug prescriptions, the progressive rise in "optimal" drug dosage and costs associated with pharmaceutical management of disease. These bioactive vegetable proteins, hydrolysates and peptides may be used in formulation of functional foods, nutraceuticals, and natural drugs because of their health benefit effects suggesting their use as an alternative in treatment of various dyslipidemias, and a potential agent for reducing cardiovascular diseases risk factors.

  15. Quantifying the impact of using Coronary Artery Calcium Score for risk categorization instead of Framingham Score or European Heart SCORE in lipid lowering algorithms in a Middle Eastern population.

    PubMed

    Isma'eel, Hussain A; Almedawar, Mohamad M; Harbieh, Bernard; Alajaji, Wissam; Al-Shaar, Laila; Hourani, Mukbil; El-Merhi, Fadi; Alam, Samir; Abchee, Antoine

    2015-10-01

    The use of the Coronary Artery Calcium Score (CACS) for risk categorization instead of the Framingham Risk Score (FRS) or European Heart SCORE (EHS) to improve classification of individuals is well documented. However, the impact of reclassifying individuals using CACS on initiating lipid lowering therapy is not well understood. We aimed to determine the percentage of individuals not requiring lipid lowering therapy as per the FRS and EHS models but are found to require it using CACS and vice versa; and to determine the level of agreement between CACS, FRS and EHS based models. Data was collected for 500 consecutive patients who had already undergone CACS. However, only 242 patients met the inclusion criteria and were included in the analysis. Risk stratification comparisons were conducted according to CACS, FRS, and EHS, and the agreement (Kappa) between them was calculated. In accordance with the models, 79.7% to 81.5% of high-risk individuals were down-classified by CACS, while 6.8% to 7.6% of individuals at intermediate risk were up-classified to high risk by CACS, with slight to moderate agreement. Moreover, CACS recommended treatment to 5.7% and 5.8% of subjects untreated according to European and Canadian guidelines, respectively; whereas 75.2% to 81.2% of those treated in line with the guidelines would not be treated based on CACS. In this simulation, using CACS for risk categorization warrants lipid lowering treatment for 5-6% and spares 70-80% from treatment in accordance with the guidelines. Current strong evidence from double randomized clinical trials is in support of guideline recommendations. Our results call for a prospective trial to explore the benefits/risks of a CACS-based approach before any recommendations can be made.

  16. The value of surrogate markers to monitor cholesterol absorption, synthesis and bioconversion to bile acids under lipid lowering therapies.

    PubMed

    Stellaard, Frans; von Bergmann, Klaus; Sudhop, Thomas; Lütjohann, Dieter

    2017-05-01

    Regulation of cholesterol (Chol) homeostasis is controlled by three main fluxes, i.e. intestinal absorption, de novo synthesis (ChS) and catabolism, predominantly as bile acid synthesis (BAS). High serum total Chol and LDL-Chol concentrations in particular are considered risk factors and markers for the development of atherosclerosis. Pharmaceutical treatments to lower serum Chol have focused on reducing absorption or ChS and increasing BAS. Monitoring of these three parameters is complex involving isotope techniques, cholesterol balance experiments and advanced mass spectrometry based analysis methods. Surrogate markers were explored that require only one single fasting blood sample collection. These markers were validated in specific, mostly physiological conditions and during statin treatment to inhibit ChS. They were also applied under cholesterol absorption restriction, but were not validated in this condition. We retrospectively evaluated the use of serum campesterol (Camp), sitosterol (Sit) and cholestanol (Cholol) as markers for cholesterol absorption, lathosterol (Lath) as marker for ChS and 7α-hydroxycholesterol (7α-OH-Ch) and 27-hydroxycholesterol (27-OH-Ch) as markers for BAS under conditions of Chol absorption restriction. Additionally, their values were corrected for Chol concentration (R_sterol or oxysterols). Thirty-seven healthy male omnivore subjects were studied under treatments with placebo (PLAC), ezetimibe (EZE) to inhibit cholesterol absorption, simvastatin (SIMVA) to reduce cholesterol synthesis and a combination of both (EZE+SIMVA). Results were compared to those obtained in 18 pure vegetarian subjects (vegans) whose dietary Chol intake is extremely low. Relative or fractional Chol absorption (FrChA) was measured with the continuous feeding stable isotope procedure, ChS and BAS with the cholesterol balance method. The daily Chol intake (DICh) was inventoried and the daily Chol absorption (DACh) calculated. Monitoring cholesterol absorption, R_Camp, R_Sit and R_Cholol responded sensitively to changes in FrChA. R_Camp correlated well with FrChA in all omnivore treatment groups and in the vegan group. R_Camp confirmed reduced FrChA under EZE treatment and reduced DACh in the vegan subjects. R_Sit and R_Cholol did not accurately reflect FrChA or DACh in all situations. Monitoring endogenous cholesterol synthesis, R_Lath correlated with ChS in the vegan group, but in none of the omnivore treatment groups. R_Lath confirmed increased ChS under EZE treatment and was reduced under SIMVA treatment, while ChS was not. An increased ChS under EZE+SIMVA treatment could not be confirmed with R_Lath. R_Lath responded very insensitively to a change in ChS. Monitoring BAS, R_7α-OH-Ch but not R_27-OH-Ch correlated with BAS during PLAC, EZE and SIMVA treatments. In line with BAS, R_7α-OH-Ch did not differ in any of the omnivore treatment groups. R_7α-OH-Ch responded insensitively to a change in BAS. Under Chol absorption restriction, serum R_Camp is a sensitive and valid marker to monitor FrChA in a population with a normal DICh. Also, major changes in DACh can be detected in vegans. Serum R_Lath does not reflect ChS measured with the cholesterol balance method during EZE treatment. This result initiates the question whether the measured ChS reflects pure de novo synthesis. Serum R_7α-OH-Ch appears to be a valid but insensitive marker for BAS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. The Efficacy of Intense Pulsed Light Therapy in Postoperative Recovery from Eyelid Surgery.

    PubMed

    Linkov, Gary; Lam, Vincent B; Wulc, Allan E

    2016-05-01

    The purpose of this study was to evaluate the efficacy of postoperative intense pulsed light therapy on patients who undergo bilateral eyelid surgery. Patients presenting over a 3-month period for bilateral eyelid surgery were asked to participate in an institutional review board-approved study. Intense pulsed light therapy was administered three times to the same randomly assigned side on postoperative days 1 to 2, 5 to 7, and 10 to 12. Sham light therapy was administered to the contralateral side. Patient surveys and physician ratings were obtained based on photographic evaluation of ecchymosis, edema, and erythema. Three physicians, including the senior author (A.E.W.), submitted ratings, and these ratings were assessed for interobserver reliability. Twenty-eight patients who underwent bilateral eyelid surgery followed by intense pulsed light therapy were enrolled. The mean age of the patients was 66 years (range, 44 to 81 years). Eighty-six percent of patients were female. The change in ratings between postoperative days 1 to 2 and 10 to 12, in the treatment and control groups, was statistically significant for severity of bruising by both patient and physician assessment and for color of bruising only by patient assessment. The interobserver reliability reached the greatest agreement in the ecchymosis category at each time point for the treatment group. In a series of patients who underwent eyelid surgery, intense pulsed light therapy decreased the degree of ecchymosis compared with sham treatment in postoperative eyelid surgery patients. Therapeutic, II.

  18. An individualized intermittent intensive physical therapy schedule for a child with spastic quadriparesis.

    PubMed

    Rahlin, Mary

    2011-10-01

    Current research literature supports the use of intensive physical therapy (PT) for children with cerebral palsy (CP) but lacks consensus on the selection of a specific therapy schedule. The purpose of this case report was to describe the use of an individualized intermittent intensive PT schedule for a child with CP who was otherwise seen following a traditional, two times per week, schedule. The patient was a 4.5-year-old girl with spastic quadriparesis, GMFCS level III. The new schedule was tried over a 3-month period. Each of the 3 months included a 2-week, five times per week intensive therapy phase, followed by a 2-week resting phase. Outcomes were assessed by using the GMFM-66 and by documenting the attainment of functional gross motor skills related to the patient's PT goals. Intervention included TAMO therapy and family instruction. The patient demonstrated a gradual increase in GMFM-66 scores throughout the 9-month period covered by this case report, with the greatest mean change score obtained when the intermittent intensive therapy schedule was used. Acquired skills were retained and even improved during the resting phases. The child's parents expressed their interest in using the new PT schedule in the future.

  19. A Randomized Controlled Trial of 7-Day Intensive and Standard Weekly Cognitive Therapy for PTSD and Emotion-Focused Supportive Therapy

    PubMed Central

    Ehlers, Anke; Hackmann, Ann; Grey, Nick; Wild, Jennifer; Liness, Sheena; Albert, Idit; Deale, Alicia; Stott, Richard; Clark, David M.

    2014-01-01

    Objective Psychological treatments for posttraumatic stress disorder (PTSD) are usually delivered once or twice weekly over several months. It is unclear whether they can be successfully delivered over a shorter period of time. This clinical trial had two goals, (1) to investigate the acceptability and efficacy of a 7-day intensive version of cognitive therapy for PTSD, and (2) to investigate whether cognitive therapy has specific treatment effects by comparing intensive and standard weekly cognitive therapy with an equally credible alternative treatment. Method Patients with chronic PTSD (N=121) were randomly allocated to 7-day intensive or standard 3-month weekly cognitive therapy for PTSD, 3-month weekly emotion-focused supportive therapy, or a 14-week waitlist condition. Primary outcomes were PTSD symptoms and diagnosis as assessed by independent assessors and self-report. Secondary outcomes were disability, anxiety, depression, and quality of life. Measures were taken at initial assessment, 6 weeks and 14 weeks (post-treatment/wait). For groups receiving treatment, measures were also taken at 3 weeks, and follow-ups at 27 and 40 weeks after randomization. All analyses were intent-to-treat. Results At post-treatment/wait assessment, 73%, 77%, 43%, 7% of the intensive cognitive therapy, standard cognitive therapy, supportive therapy, and waitlist groups, respectively, had recovered from PTSD. All treatments were well tolerated and were superior to waitlist on all outcome measures, with the exception of no difference between supportive therapy and waitlist on quality of life. For primary outcomes, disability and general anxiety, intensive and standard cognitive therapy were superior to supportive therapy. Intensive cognitive therapy achieved faster symptom reduction and comparable overall outcomes to standard cognitive therapy. Conclusions Cognitive therapy for PTSD delivered intensively over little more than a week is as effective as cognitive therapy delivered

  20. [Interaction between APOB gene polymorphism and risk factors in coronary heart disease patients without lipid-lowering treatment].

    PubMed

    Pu, T; Yu, H Y; Xu, M; Zhang, Y; Yan, H; Sun, L J; Xu, W X; Zhang, Y Y; Gao, W

    2017-05-24

    Objective: To investigate the association between APOB gene R532W polymorphism and the risk of coronary heart disease (CHD) in patients without lipid-lowering treatment and to analyze the interactions between the variation of R532W and different risk factors of CHD. Methods: CHD and non-CHD were diagnosed according to coronary artery angiography (CAG) and/or coronary computed tomography angiogram (CTA) results, as well as clinical features. Blood samples from 771 CHD patients and 772 age- and sex-matched non-CHD controls, who never accepted any lipid-lowering treatments, were collected. R532W was genotyped by HumanExome BeadChip at BGI and strict quality control was made. Firstly, the association between R532W polymorphism and the risk of CHD in 3 genetic models (GA+ AA vs.GG, AA vs. GG+ GA, AA vs. GA vs. GG) after adjusting confounding factors was explored. Then, the interactions between the variation of this loci and risk factors related to CHD were investigated. Results: (1) Total cholesterol (TC) levels were significantly lower in AA genotype than in GA genotype in the total cohort and non-CHD controls, but was similar among the 3 genotypes in CHD patients. (2) R532W GG, GA and AA distribution was 80.7%, 18.2% and 1.2% in CHD patients, and 74.6%, 23.8% and 1.6% in non-CHD controls (P<0.05). (3) R532 polymorphism was related to the incidence of CHD in the dominant model, and A-allele carriers were related to about 35% reduced risk of CHD (OR=0.653, 95% CI 0.502-0.849, P=0.001) after adjusting for confounding factors. (4) R532W polymorphism had positive interactions with hypertension (1.452) and smoke (1.077), while negative interaction with diabetes (0.553) in the occurrence of CHD. Conclusions: APOB gene R532W polymorphism is related to TC levels in Chinese north Han population. A-allele carries of R532W loci is linked with reduced risk of CHD in the absence of lipid-lowering treatment. R532W polymorphism has a positive additive interaction with hypertension

  1. G5-PEG PAMAM dendrimer incorporating nanostructured lipid carriers enhance oral bioavailability and plasma lipid-lowering effect of probucol.

    PubMed

    Qi, Rong; Li, Yan-Zhi; Chen, Cong; Cao, Yi-Ni; Yu, Mao-Mao; Xu, Lu; He, Bing; Jie, Xu; Shen, Wen-Wen; Wang, Yu-Nan; van Dongen, Mallory A; Liu, Guo-Qing; Banaszak Holl, Mark M; Zhang, Qiang; Ke, Xue

    2015-07-28

    This work aimed to improve the oral bioavailability and plasma lipid-lowering effect of probucol (PB) by constructing a combined drug delivery system (CDDS) composed of nanostructured lipid carrier (NLC) and PEGylated poly(amidoamine) dendrimer (PEG-PAMAM). PEG-PAMAM with dendrimer generations of 5 (G5-PEG) or 7 (G7-PEG) were incorporated in PB-NLCs to form PB-CDDSs, PB-NLCs/G5-PEG and PB-NLCs/G7-PEG. The resultant two kinds of PB-CDDSs were characterized by particle size, zeta potential, drug encapsulation efficacy, PB release rates, and physical stability. Formulation effects of NLC and CDDS on the cellular uptake of hydrophobic drug were explored in Caco-2 cells by fluorescent Cy5 dye as a hydrophobic drug model. Furthermore, in vivo pharmacokinetics of the PB-CDDS composed of G5-PEG and PB-NLCs were investigated in a low density lipoprotein receptor knockout (LDLr-/-) mouse model, including plateau plasma PB concentrations after oral administration of multiple doses, and bioavailability after oral administration of a single dose of different PB formulations. In addition, lipid-lowering effect of PB-NLCs/G5-PEG was studied. The results indicate that both G5-PEG and G7-PEG significantly improved aqueous solubility of PB. The two PB-CDDSs exhibited similar particle size (around 150nm) as PB-NLCs, but slower PB burst release rate, higher total PB release amount, and better particle morphology and storage stability than PB-NLCs. In comparison with traditional NLC, CDDS dramatically enhanced cellular uptake of Cy5 into Caco-2 cells. In vivo results demonstrate that PB-NLCs/G5-PEG had the highest plateau plasma PB concentration and oral bioavailability, and the greatest cholesterol-lowering effect in comparison with PB suspensions and PB-NLCs. Therefore, G5-PEG incorporating NLC can be exploited as a promising drug delivery system to improve oral bioavailability and lipid-lowering effect of PB. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Association of genetic variations with pharmacokinetics and lipid-lowering response to atorvastatin in healthy Korean subjects

    PubMed Central

    Woo, Hye In; Kim, Suk Ran; Huh, Wooseong; Ko, Jae-Wook; Lee, Soo-Youn

    2017-01-01

    Background Statins are effective agents in the primary and secondary prevention of cardiovascular disease, but treatment response to statins varies among individuals. We analyzed multiple genetic polymorphisms and assessed pharmacokinetic and lipid-lowering responses after atorvastatin 80 mg treatment in healthy Korean individuals. Methods Atorvastatin 80 mg was given to 50 healthy Korean male volunteers. Blood samples were collected to measure plasma atorvastatin and lipid concentrations up to 48 hours after atorvastatin administration. Subjects were genotyped for 1,936 drug metabolism and transporter genetic polymorphisms using the Affymetrix DMET plus array. Results The pharmacokinetics and lipid-lowering effect of atorvastatin showed remarkable interindividual variation. Three polymorphisms in the SLCO1B1, SLCO1B3, and ABCC2 genes were associated with either the maximum concentration (Cmax) of atorvastatin or changes in total cholesterol or low-density lipoprotein cholesterol (LDL-C). Minor homozygotes (76.5 ng/mL) of SLCO1B1 c.-910G>A showed higher Cmax than heterozygotes (34.0 ng/mL) and major homozygotes (33.5 ng/mL, false discovery rate P=0.040). Cmax and the area under the plasma concentration curve from hour 0 to infinity (AUC∞) were higher in carriers of the SLCO1B1*17 haplotype that included c.-910G>A than in noncarriers (46.1 vs 32.8 ng/mL for Cmax; 221.5 vs 154.2 ng/mL for AUC∞). SLCO1B3 c.334G>T homozygotes (63.0 ng/mL) also showed higher Cmax than heterozygotes (34.7 ng/mL) and major homozygotes (31.4 ng/mL, FDR P=0.037). A nonsynonymous ABCC2 c.1249G>A was associated with small total cholesterol and LDL-C responses (0.23% and −0.70% for G/A vs −11.9% and −17.4% for G/G). The Cmax tended to increase according to the increase in the number of minor allele of SLCO1B1 c. −910G>A and SLCO1B3 c.334G>T. Conclusion Genetic polymorphisms in transporter genes, including SLCO1B1, SLCO1B3, and ABCC2, may influence the pharmacokinetics and lipid-lowering

  3. Hypercalcemia in the Intensive Care Unit: A Review of Pathophysiology, Diagnosis, and Modern Therapy.

    PubMed

    Maier, Joshua D; Levine, Steven N

    2015-07-01

    Hypercalcemia may be seen in a variety of clinical settings and often requires intensive management when serum calcium levels are dramatically elevated. All of the many etiologies of mild hypercalcemia can lead to severe hypercalcemia. Knowledge of the physiologic mechanisms involved in maintaining normocalcemia and basic pathophysiology is essential for making a timely diagnosis and hence prompt institution of etiology-specific therapy. The development of new medications and critical reviews of traditional therapies have changed the treatment paradigm for severe hypercalcemia, calling for a more limited role for aggressive isotonic fluid administration and furosemide and an expanded role for calcitonin and the bisphosphonates. Experimental therapies such as denosumab show promise.

  4. Comparison of High-Intensity Laser Therapy and Ultrasound Treatment in the Patients with Lumbar Discopathy

    PubMed Central

    Boyraz, Ismail; Yildiz, Ahmet; Koc, Bunyamin

    2015-01-01

    The aim of the present study was to evaluate the efficiency of high intensity laser and ultrasound therapy in patients who were diagnosed with lumbar disc herniation and who were capable of performing physical exercises. 65 patients diagnosed with lumbar disc were included in the study. The patients were randomly divided into three groups: Group 1 received 10 sessions of high intensity laser to the lumbar region, Group 2 received 10 sessions of ultrasound, and Group 3 received medical therapy for 10 days and isometric lumbar exercises. The efficacy of the treatment modalities was compared with the assessment of the patients before the therapy at the end of the therapy, and in third month after the therapy. Comparing the changes between groups, statically significant difference was observed in MH (mental health) parameter before treatment between Groups 1 and 2 and in MH parameter and VAS score in third month of the therapy between Groups 2 and 3. However, the evaluation of the patients after ten days of treatment did not show significant differences between the groups compared to baseline values. We found that HILT, ultrasound, and exercise were efficient therapies for lumbar discopathy but HILT and ultrasound had longer effect on some parameters. PMID:25883952

  5. [Intensity-modulated radiation therapy and stereotactic body radiation therapy for head and neck tumors: evidence-based medicine].

    PubMed

    Lapierre, A; Martin, F; Lapeyre, M

    2014-10-01

    Over the last decade, there have been many technical advances in radiation therapy, such as the spread of intensity-modulated conformal radiotherapy, and the rise of stereotactic body radiation therapy. By allowing better dose-to-target conformation and thus better organs at risk-sparing, these techniques seem very promising, particularly in the field of head and neck tumors. The present work aims at analyzing the level of evidence and recommendation supporting the use of high-technology radiotherapy in head and neck neoplasms, by reviewing the available literature.

  6. Ethanolic Extract of Vitis thunbergii Exhibits Lipid Lowering Properties via Modulation of the AMPK-ACC Pathway in Hypercholesterolemic Rabbits

    PubMed Central

    Pan, Chun-Hsu; Tsai, Chia-Hua; Lin, Wen-Hsin; Chen, Guo-Yan; Wu, Chieh-Hsi

    2012-01-01

    Vitis thunbergii (VT) is a wild grape that has been shown to provide various cardioprotective effects. The present study was designed to examine whether a VT extract could reduce serum lipid levels and prevent atherogenesis in a hypercholesterolemic rabbit model. At the end of an 8-week study, our results showed that a VT extract supplement markedly suppressed the serum levels of cholesterol and low-density lipoprotein, reduced lipid accumulation in liver tissues, and limited aortic fatty streaks. Our findings suggest that the VT extract activated AMPK (5′-adenosine monophosphate-activated protein kinase) with subsequent inhibition of the activation of ACC (acetyl-CoA carboxylase). Our results suggest that this VT extract could be further developed as a potential lipid-lowering agent and as a natural health food to prevent atherogenesis. PMID:22536284

  7. Long-term administration of inulin-type fructans has no significant lipid-lowering effect in normolipidemic humans.

    PubMed

    Forcheron, Fabien; Beylot, Michel

    2007-08-01

    Short-term studies have shown that the addition to diet of inulin-type fructans, a nondigestible carbohydrate, may have a plasma lipid-lowering effect in humans. Whether this beneficial effect persists during long-term administration has not been determined. The study was aimed at determining whether a prolonged (6 months) administration of inulin-type fructans to healthy subjects has a lipid-lowering action. In a double-blind, randomized, placebo-controlled study, 17 healthy subjects were studied before and after 6 months of daily administration of placebo (8 subjects) or 10 g of a mix of inulin and oligofructose (9 subjects). During this 6-month period, they consumed their usual diet and did not modify their everyday way of life. We measured plasma lipid concentrations; cholesterol synthesis and hepatic lipogenesis; and adipose tissue and circulating mononuclear cell messenger RNA concentrations of key regulatory genes of cholesterol metabolism. Compared with the administration of placebo, the administration of inulin-type fructans had no effect on plasma triacylglycerol concentrations and hepatic lipogenesis and induced only a nonsignificant trend for decreased plasma total and low-density lipoprotein cholesterol levels and increased high-density lipoprotein cholesterol concentration. Cholesterol synthesis was not significantly modified. Of all the messenger RNA concentrations measured, none was significantly modified by the administration of inulin-type fructans. In conclusion, contrary to what was observed in short-term studies, we observed no significant beneficial effect of a long-term (6-month) administration of inulin-type fructans on plasma lipids in healthy human subjects.

  8. Lipid-Lowering Effects of Tetradecylthioacetic Acid in Antipsychotic-Exposed, Female Rats: Challenges with Long-Term Treatment

    PubMed Central

    Skrede, Silje; Fernø, Johan; Bjørndal, Bodil; Brede, Wenche Rødseth; Bohov, Pavol; Berge, Rolf Kristian; Steen, Vidar Martin

    2012-01-01

    Background Psychiatric patients often require chronic treatment with antipsychotic drugs, and while rats are frequently used to study antipsychotic-induced metabolic adverse effects, long-term exposure has only partially mimicked the appetite-stimulating and weight-inducing effects found in the clinical setting. Antipsychotic-induced effects on serum lipids are also inconsistent in rats, but in a recent study we demonstrated that subchronic treatment with the orexigenic antipsychotic olanzapine resulted in weight-independent increase in serum triglycerides and activation of lipogenic gene expression in female rats. In addition, a recent long-term study in male rats showed that chronic treatment with antipsychotic drugs induced dyslipidemic effects, despite the lack of weight gain. Aims In the current study, we sought to examine long-term effects of antipsychotic drugs on weight gain, lipid levels and lipid composition after twice-daily administration of antipsychotics to female rats, and to investigate potential beneficial effects of the lipid-lowering agent tetradecylthioacetic acid (TTA), a modified fatty acid. Methods Female rats were exposed to orexigenic antipsychotics (olanzapine or clozapine), metabolically neutral antipsychotics (aripiprazole or ziprasidone), or TTA for 8 weeks. Separate groups received a combination of clozapine and TTA or olanzapine and TTA. The effects of TTA and the combination of olanzapine and TTA after 2 weeks were also investigated. Results The antipsychotic-induced weight gain and serum triglyceride increase observed in the subchronic setting was not present after 8 weeks of treatment with antipsychotics, while lipid-lowering effect of TTA was much more pronounced in the chronic than in the subchronic setting, with concomitant upregulation of key oxidative enzymes in the liver. Unexpectedly, TTA potentiated weight gain in rats treated with antipsychotics. Conclusion TTA is a promising candidate for prophylactic treatment of

  9. Lipid-lowering effects of tetradecylthioacetic acid in antipsychotic-exposed, female rats: challenges with long-term treatment.

    PubMed

    Skrede, Silje; Fernø, Johan; Bjørndal, Bodil; Brede, Wenche Rødseth; Bohov, Pavol; Berge, Rolf Kristian; Steen, Vidar Martin

    2012-01-01

    Psychiatric patients often require chronic treatment with antipsychotic drugs, and while rats are frequently used to study antipsychotic-induced metabolic adverse effects, long-term exposure has only partially mimicked the appetite-stimulating and weight-inducing effects found in the clinical setting. Antipsychotic-induced effects on serum lipids are also inconsistent in rats, but in a recent study we demonstrated that subchronic treatment with the orexigenic antipsychotic olanzapine resulted in weight-independent increase in serum triglycerides and activation of lipogenic gene expression in female rats. In addition, a recent long-term study in male rats showed that chronic treatment with antipsychotic drugs induced dyslipidemic effects, despite the lack of weight gain. In the current study, we sought to examine long-term effects of antipsychotic drugs on weight gain, lipid levels and lipid composition after twice-daily administration of antipsychotics to female rats, and to investigate potential beneficial effects of the lipid-lowering agent tetradecylthioacetic acid (TTA), a modified fatty acid. Female rats were exposed to orexigenic antipsychotics (olanzapine or clozapine), metabolically neutral antipsychotics (aripiprazole or ziprasidone), or TTA for 8 weeks. Separate groups received a combination of clozapine and TTA or olanzapine and TTA. The effects of TTA and the combination of olanzapine and TTA after 2 weeks were also investigated. The antipsychotic-induced weight gain and serum triglyceride increase observed in the subchronic setting was not present after 8 weeks of treatment with antipsychotics, while lipid-lowering effect of TTA was much more pronounced in the chronic than in the subchronic setting, with concomitant upregulation of key oxidative enzymes in the liver. Unexpectedly, TTA potentiated weight gain in rats treated with antipsychotics. TTA is a promising candidate for prophylactic treatment of antipsychotic-induced dyslipidemic effects, but a

  10. Impact of coronary artery calcium on cardiovascular risk categorization and lipid-lowering drug eligibility in asymptomatic hypercholesterolemic men.

    PubMed

    Chironi, Gilles; Simon, Alain; Megnien, Jean-Louis; Sirieix, Marie-Emmanuelle; Mousseaux, Elie; Pessana, Franco; Armentano, Ricardo

    2011-09-01

    Application of coronary artery calcium (CAC) for stratifying coronary heart disease (CHD) risk may change the proportion of subjects eligible for risk reduction treatment and decrease cost-effectiveness of primary prevention. We therefore aimed to analyze the impact of CAC on CHD risk categorization. We measured CAC with electron beam computed tomography in 500 asymptomatic untreated hypercholesterolemic men and re-calibrated 10-year Framingham CHD risk by adding CAC score information (post CAC test risk) via an algorithm integrating relative risk and expected distribution of CAC in the population tested. Proportions of low (<10%), intermediate (10-20%) and high (>20%) risk categories, and of eligibility for lipid-lowering treatment, were compared between Framingham risk and post CAC test risk. In the overall population, post CAC test risk calculation changed risk categorization defined by Framingham assessment alone, with 10% more low risk and 10% less intermediate risk (p<0.01). Risk reclassifications were bidirectional since 30% of high and 30% of intermediate Framingham risk were downgraded to intermediate and low risk categories respectively, while 11% of low and 14% of intermediate Framingham risk were upgraded to intermediate and high-risk categories respectively. Post CAC test risk did not change the proportion of Framingham-based lipid-lowering treatment eligibility in the overall population but decreased it by 8% in intermediate Framingham risk subgroup (p<0.05). Addition of CAC to risk prediction resulted rather in downgrading than in upgrading risk and did not change treatment eligibility, except in intermediate risk subjects, less frequently eligible for treatment. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  11. Electrocardiographic measures of left ventricular hypertrophy in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

    PubMed

    Ernst, Michael E; Davis, Barry R; Soliman, Elsayed Z; Prineas, Ronald J; Okin, Peter M; Ghosh, Alokananda; Cushman, William C; Einhorn, Paula T; Oparil, Suzanne; Grimm, Richard H

    2016-12-01

    Left ventricular hypertrophy (LVH) predicts cardiovascular risk in hypertensive patients. We analyzed baseline/follow-up electrocardiographies in 26,376 Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial participants randomized to amlodipine (A), lisinopril (L), or chlorthalidone (C). Prevalent/incident LVH was examined using continuous and categorical classifications of Cornell voltage. At 2 and 4 years, prevalence of LVH in the C group (5.57%; 6.14%) was not statistically different from A group (2 years: 5.47%; P = .806, 4 years: 6.54%; P = .857) or L group (2 years: 5.64%; P = .857, 4 years: 6.50%; P = .430). Incident LVH followed similarly, with no difference at 2 years for C (2.99%) compared to A (2.57%; P = .173) or L (3.16%; P = .605) and at 4 years (C = 3.52%, A = 3.29%, L = 3.71%; P = .521 C vs. A, P = .618 C vs. L). Mean Cornell voltage decreased comparably across treatment groups (Δ baseline, 2 years = +3 to -27 μV, analysis of variance P = .8612; 4 years = +10 to -17 μV, analysis of variance P = .9692). We conclude that risk reductions associated with C treatment in secondary end points of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial cannot be attributed to differential improvements in electrocardiography LVH. Copyright © 2016 American Society of Hypertension. All rights reserved.

  12. Increased Intensity of Physical Therapy for a Child with Gross Motor Developmental Delay: A Case Report

    ERIC Educational Resources Information Center

    Schreiber, Joe

    2004-01-01

    Background and Purpose: The intensity of physical therapy provided for children in early intervention (EI) programs may be influenced by a number of factors. In an individualized program, however, some children and families may benefit from an increased frequency of services. The purpose of this case report was to systematically document and…

  13. Two-Day, Intensive Cognitive-Behavioral Therapy for Panic Disorder: A Case Study

    ERIC Educational Resources Information Center

    Deacon, Brett

    2007-01-01

    Cognitive-behavioral therapy (CBT) is a highly effective treatment for panic disorder. However, few patients have access to this treatment, particularly those living in rural areas. In a pilot study, the author previously described the efficacy of a 2-day, intensive, exposure-based CBT intervention that was developed for the purpose of delivering…

  14. Increased Intensity of Physical Therapy for a Child with Gross Motor Developmental Delay: A Case Report

    ERIC Educational Resources Information Center

    Schreiber, Joe

    2004-01-01

    Background and Purpose: The intensity of physical therapy provided for children in early intervention (EI) programs may be influenced by a number of factors. In an individualized program, however, some children and families may benefit from an increased frequency of services. The purpose of this case report was to systematically document and…

  15. Two-Day, Intensive Cognitive-Behavioral Therapy for Panic Disorder: A Case Study

    ERIC Educational Resources Information Center

    Deacon, Brett

    2007-01-01

    Cognitive-behavioral therapy (CBT) is a highly effective treatment for panic disorder. However, few patients have access to this treatment, particularly those living in rural areas. In a pilot study, the author previously described the efficacy of a 2-day, intensive, exposure-based CBT intervention that was developed for the purpose of delivering…

  16. Intense pulsed light therapy (IPL) induced iritis following treatment for a medial canthal capillary malformation.

    PubMed

    Crabb, Matthew; Chan, Weng Onn; Taranath, Deepa; Huilgol, Shyamala C

    2014-11-01

    The popularity of intense pulsed light (IPL) therapy continues to increase due to its relative safety, high skin coverage rate and ability to treat both vascular and pigmented lesions. An often-overlooked risk is the potential for IPL-induced ocular damage. The damage sustained can cause significant, persistent morbidity and can occur even with very limited IPL exposure to the eye.

  17. Prospective, noninterventional, uncontrolled, open-chart, pharmacoepidemiologic study of prescribing patterns for lipid-lowering drugs at a tertiary care teaching hospital in North India.

    PubMed

    Goyal, Pankaj; Sharma, Geeta; Bal, Baljinderpal S; Singh, Jatinder; Singh, Jagjit; Randhawa, Gurpreet Kaur; Pandhi, Shaloo; Sharma, Rohit

    2002-12-01

    The guidelines for management of dyslipidemia released by the US National Cholesterol Education Program (NCEP) have been questioned for their relevance in the South Asian Indian populations because these populations are reported to have significantly different lipoprotein parameters and atherogenic risk factors than Western populations. The aim of this study was to determine current prescribing patterns for lipid-lowering drugs (LLDs) adopted by physicians in North India. This prospective, noninterventional, uncontrolled, open-chart, pharmacoepidemiologic study was conducted from June 2000 to August 2000 at a tertiary care hospital in North India and included 200 dyslipidemic patients. The pattern of prescribing LLDs was recorded, along with the serum levels of lipid parameters-total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and lipoprotein(a) (Lp[a])-at the time of initiating LLD therapy and compared with the 1993 NCEP-II therapeutic guidelines for dyslipidemia management. The mean (SD) levels of lipid parameters in the study population were as follows: TC, 223.2 (21.5) mg/dL; TG, 258.4 (61.3) mg/dL; LDL-C, 131.6 (26.5) mg/dL; HDL-C, 39.8 (8.9) mg/dL; and Lp(a), 44.8 (26.8) mg/dL. The LLDs prescribed were fibrates (53.5%) and statins (46.5%). Forty percent of patients prescribed LLDs did not meet the NCEP-II criteria for initiation of LLD therapy. Considerable differences in prescribing patterns of LLDs were observed compared with the then-prevalent NCEP-II guidelines. However, due to the abnormally high serum Lp(a) levels present in the average dyslipidemia profile in South Asian Indian populations, this pattern was in accordance with the specific recommendations made for these populations, as well as with the 2001 NCEP-III guidelines.

  18. Associations between intensive diabetes therapy and NMR-determined lipoprotein subclass profiles in type 1 diabetes.

    PubMed

    Zhang, Ying; Jenkins, Alicia J; Basu, Arpita; Stoner, Julie A; Lopes-Virella, Maria F; Klein, Richard L; Lyons, Timothy J

    2016-02-01

    Our objective is to define differences in circulating lipoprotein subclasses between intensive versus conventional management of type 1 diabetes during the randomization phase of the Diabetes Control and Complications Trial (DCCT). NMR-determined lipoprotein subclass profiles (NMR-LSPs), which estimate molar subclass concentrations and mean particle diameters, were determined in 1,294 DCCT subjects after a median of 5 years (interquartile range: 4-6 years) of randomization to intensive or conventional diabetes management. In cross-sectional analyses, we compared standard lipids and NMR-LSPs between treatment groups. Standard total, LDL, and HDL cholesterol levels were similar between randomization groups, while triglyceride levels were lower in the intensively treated group. NMR-LSPs showed that intensive therapy was associated with larger LDL diameter (20.7 vs. 20.6 nm, P = 0.01) and lower levels of small LDL (median: 465 vs. 552 nmol/l, P = 0.007), total IDL/LDL (mean: 1,000 vs. 1,053 nmol/l, P = 0.01), and small HDL (mean: 17.3 vs. 18.6 μmol/l, P < 0.0001), the latter accounting for reduced total HDL (mean: 33.8 vs. 34.8 μmol/l, P = 0.01). In conclusion, intensive diabetes therapy was associated with potentially favorable changes in LDL and HDL subclasses in sera. Further research will determine whether these changes contribute to the beneficial effects of intensive diabetes management on vascular complications.

  19. Nurse-coordinated care improves the achievement of LDL cholesterol targets through more intensive medication titration.

    PubMed

    Snaterse, Marjolein; Jorstad, Harald T; Heiligenberg, Marlies; Ter Riet, Gerben; Boekholdt, S Matthijs; Scholte Op Reimer, Wilma; Peters, Ron J

    2017-01-01

    Nurse-coordinated care (NCC) improves the achievement of low-density lipoprotein-cholesterol (LDL-C) targets after an acute coronary syndrome (ACS). We hypothesised that NCC improves achievement of LDL-C targets through more intensive medication titration. We used data from Randomised Evaluation of Secondary Prevention by Outpatient Nurse Specialists (RESPONSE), a multicentre randomised trial on the efficacy of NCC in 754 ACS patients. Follow-up data were collected at 6 and 12 months. To enable comparison between the various types and dosages of statins, we used the average lipid-lowering potency (ALLP, % LDL-C lowering) as an indicator of lipid-lowering medication intensity. Most patients in NCC intervention and usual care groups (96%) had started lipid-lowering therapy during the index hospitalisation. At 6 months, titration activities (up or down) were applied in 45% of NCC patients compared with 24% of patients receiving usual care (p<0.001), and a difference was also seen at 12 months follow-up (52% vs 34%, p<0.001). In patients not on LDL-C target at baseline, titration activities at 6 months were recorded in 63% and 30% of NCC and usual care patients respectively (p<0.001), with increased titration activities in both groups at 12 months (69% vs 43%, p<0.001). NCC is associated with more frequent and intense lipid-lowering medication titration to reach LDL-C targets as compared with usual care alone. Further, merely starting the guideline-recommended dose is insufficient to reach the guideline-recommended LDL-C target level. TC1290 (Netherlands).

  20. Nurse-coordinated care improves the achievement of LDL cholesterol targets through more intensive medication titration

    PubMed Central

    Snaterse, Marjolein; Jorstad, Harald T; Heiligenberg, Marlies; ter Riet, Gerben; Boekholdt, S Matthijs; Scholte op Reimer, Wilma; Peters, Ron J

    2017-01-01

    Background Nurse-coordinated care (NCC) improves the achievement of low-density lipoprotein-cholesterol (LDL-C) targets after an acute coronary syndrome (ACS). We hypothesised that NCC improves achievement of LDL-C targets through more intensive medication titration. Methods We used data from Randomised Evaluation of Secondary Prevention by Outpatient Nurse Specialists (RESPONSE), a multicentre randomised trial on the efficacy of NCC in 754 ACS patients. Follow-up data were collected at 6 and 12 months. To enable comparison between the various types and dosages of statins, we used the average lipid-lowering potency (ALLP, % LDL-C lowering) as an indicator of lipid-lowering medication intensity. Results Most patients in NCC intervention and usual care groups (96%) had started lipid-lowering therapy during the index hospitalisation. At 6 months, titration activities (up or down) were applied in 45% of NCC patients compared with 24% of patients receiving usual care (p<0.001), and a difference was also seen at 12 months follow-up (52% vs 34%, p<0.001). In patients not on LDL-C target at baseline, titration activities at 6 months were recorded in 63% and 30% of NCC and usual care patients respectively (p<0.001), with increased titration activities in both groups at 12 months (69% vs 43%, p<0.001). Conclusion NCC is associated with more frequent and intense lipid-lowering medication titration to reach LDL-C targets as compared with usual care alone. Further, merely starting the guideline-recommended dose is insufficient to reach the guideline-recommended LDL-C target level. Trial Registration number TC1290 (Netherlands). PMID:28761680

  1. Correlation between Ultrasound Reflection Intensity and Tumor Ablation Ratio of Late-Stage Pancreatic Carcinoma in HIFU Therapy: Dynamic Observation on Ultrasound Reflection Intensity

    PubMed Central

    Ge, Hui-Yu; Miao, Li-Ying; Wang, Jin-Rui; Xiong, Liu-Lin; Yan, Fang; Zheng, Cui-Shan; Jia, Jian-Wen; Cui, Li-Gang; Chen, Wen

    2013-01-01

    The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma. PMID:24453916

  2. Correlation between ultrasound reflection intensity and tumor ablation ratio of late-stage pancreatic carcinoma in HIFU therapy: dynamic observation on ultrasound reflection intensity.

    PubMed

    Ge, Hui-Yu; Miao, Li-Ying; Wang, Jin-Rui; Xiong, Liu-Lin; Yan, Fang; Zheng, Cui-Shan; Jia, Jian-Wen; Cui, Li-Gang; Chen, Wen

    2013-01-01

    The minimally invasive high-intensity focused ultrasound (HIFU) therapy is thermal ablation treatment for late-stage pancreatic carcinoma with widely recognized safety and effectiveness, but there are currently no instant assessment methods for its ablation effect. It is vital to find a real-time high-sensitive assessment method. This research aims to dynamically observe the variation rules of ultrasound reflection intensity, analyze the correlation between ultrasound reflection intensity and tumor ablation ratio, and find out the value of ultrasound reflection intensity in prognosis of HIFU ablation effect. HIFU intermittent therapies were retrospectively analyzed for 31 subjects with late-stage pancreatic carcinoma from March 2007 to December 2009 in the study. The variation rules of the ultrasound reflection intensity during HIFU therapy were summarized and the correlation between ultrasound reflection intensity and tumor ablation ratio was analyzed based on the tumor ablation ratio indicated by CT scanning. The conclusion is that variation of ultrasound reflection intensity can be used for initial assessment of tumor ablation in HIFU therapy and early prognosis of overall HIFU ablation, providing important clinical basis for improving safety and effectiveness of HIFU therapy. Ultrasound can work as a real-time imaging instrument for observation of HIFU ablation effect in treating late-stage pancreatic carcinoma.

  3. Thyroid storm after intensity-modulated radiation therapy: a case report and discussion.

    PubMed

    Diaz, Roberto; Blakey, Marc D; Murphy, Patrick B; Cryar, A Keith; Cmelak, Anthony J

    2009-03-01

    A 43-year-old man with locally advanced squamous cell carcinoma of the base of tongue was treated with induction chemotherapy followed by intensity-modulated radiation therapy (IMRT). Within 20 days post-treatment, the patient developed clinical symptoms highly suggestive of hyperthyroidism. Two and one half months after completion of therapy, the patient developed severe thyrotoxicosis, which, in retrospect, appears to have met the criteria for thyroid storm. This case history illustrates a previously unreported, life-threatening complication of external-beam radiation that should be considered in patients receiving IMRT therapy involving the thyroid. Diagnosis of the patient's hyperthyroidism and probable thyroid storm was difficult to recognize because of the significant overlap between the signs and symptoms of severe thyrotoxicosis and the expected toxicities of his cancer therapy.

  4. Defining and Treating Older Adults with Acute Myeloid Leukemia Who Are Ineligible for Intensive Therapies

    PubMed Central

    Pettit, Kristen; Odenike, Olatoyosi

    2015-01-01

    Although acute myeloid leukemia (AML) is primarily a disease of older adults (age ≥60 years), the optimal treatment for older adults remains largely undefined. Intensive chemotherapy is rarely beneficial for frail older adults or those with poor-risk disease, but criteria that define fitness and/or appropriateness for intensive chemotherapy remain to be standardized. Evaluation of disease-related and patient-specific factors in the context of clinical decision making has therefore been largely subjective. A uniform approach to identify those patients most likely to benefit from intensive therapies is needed. Here, we review currently available objective measures to define older adults with AML who are ineligible for intensive chemotherapy, and discuss promising investigational approaches. PMID:26697412

  5. Comparative effectiveness of focused shock wave therapy of different intensity levels and radial shock wave therapy for treating plantar fasciitis: a systematic review and network meta-analysis.

    PubMed

    Chang, Ke-Vin; Chen, Ssu-Yuan; Chen, Wen-Shiang; Tu, Yu-Kang; Chien, Kuo-Liong

    2012-07-01

    To compare the effectiveness of focused shock wave (FSW) therapy of different intensity levels and a new alternative, radial shock wave (RSW) for managing plantar fasciitis. Electronic databases including MEDLINE and PubMed were searched from January 1996 to June 2011. Randomized controlled trials comparing shock wave and placebo therapy were included. Two reviewers independently scrutinized eligible articles, and disagreement was resolved by discussion. Literature searching identified 93 nonduplicate citations, of which 12 trials comprising 1431 participants were included. Information, such as patient characteristics, shock wave intensity, and outcome measures, was extracted by 1 reviewer and checked by another. Both reviewers assessed the trials' quality by using the Jadad scale. FSW therapy of different intensity ranges was treated as 3 subgroups, whereas studies using RSW therapy were regarded as a separate group. The success rates of treatment and pain reduction magnitudes were used as the outcomes. The traditional meta-analysis showed that medium and high-intensity FSW therapy had reliably higher success rates and pain reduction than the placebo, while the effectiveness of low-intensity FSW therapy and RSW therapy appeared less convincing because of very large confidence intervals. After employing network meta-analysis, the probability of being the best therapy was the highest in RSW therapy, followed by low-, medium-, or high-intensity FSW therapy. The meta-regression indicated that the success rate of FSW therapy was not related to its intensity, whereas elevated energy efflux densities tended to relieve pain more. Setting the highest and mostly tolerable energy output within medium intensity ranges is the ideal option when applying FSW therapy on plantar fasciitis. RSW therapy is considered an appropriate alternative because of its lower price and probably better effectiveness. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by

  6. Robust plan optimization using edge-enhanced intensity for intrafraction organ deformation in prostate intensity-modulated radiation therapy

    PubMed Central

    Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Tamari, Keisuke; Seo, Yuji; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2017-01-01

    This study evaluated a method for prostate intensity-modulated radiation therapy (IMRT) based on edge-enhanced (EE) intensity in the presence of intrafraction organ deformation using the data of 37 patients treated with step-and-shoot IMRT. On the assumption that the patient setup error was already accounted for by image guidance, only organ deformation over the treatment course was considered. Once the clinical target volume (CTV), rectum, and bladder were delineated and assigned dose constraints for dose optimization, each voxel in the CTV derived from the DICOM RT-dose grid could have a stochastic dose from the different voxel location according to the probability density function as an organ deformation. The stochastic dose for the CTV was calculated as the mean dose at the location through changing the voxel location randomly 1000 times. In the EE approach, the underdose region in the CTV was delineated and optimized with higher dose constraints that resulted in an edge-enhanced intensity beam to the CTV. This was compared to a planning target volume (PTV) margin (PM) approach in which a CTV to PTV margin equivalent to the magnitude of organ deformation was added to obtain an optimized dose distribution. The total monitor units, number of segments, and conformity index were compared between the two approaches, and the dose based on the organ deformation of the CTV, rectum, and bladder was evaluated. The total monitor units, number of segments, and conformity index were significantly lower with the EE approach than with the PM approach, while maintaining the dose coverage to the CTV with organ deformation. The dose to the rectum and bladder were significantly reduced in the EE approach compared with the PM approach. We conclude that the EE approach is superior to the PM with regard to intrafraction organ deformation. PMID:28282417

  7. Radiation-Induced Cancers From Modern Radiotherapy Techniques: Intensity-Modulated Radiotherapy Versus Proton Therapy

    SciTech Connect

    Yoon, Myonggeun; Ahn, Sung Hwan; Kim, Jinsung; Shin, Dong Ho; Park, Sung Yong; Lee, Se Byeong; Shin, Kyung Hwan; Cho, Kwan Ho

    2010-08-01

    Purpose: To assess and compare secondary cancer risk resulting from intensity-modulated radiotherapy (IMRT) and proton therapy in patients with prostate and head-and-neck cancer. Methods and Materials: Intensity-modulated radiotherapy and proton therapy in the scattering mode were planned for 5 prostate caner patients and 5 head-and-neck cancer patients. The secondary doses during irradiation were measured using ion chamber and CR-39 detectors for IMRT and proton therapy, respectively. Organ-specific radiation-induced cancer risk was estimated by applying organ equivalent dose to dose distributions. Results: The average secondary doses of proton therapy for prostate cancer patients, measured 20-60cm from the isocenter, ranged from 0.4 mSv/Gy to 0.1 mSv/Gy. The average secondary doses of IMRT for prostate patients, however, ranged between 3 mSv/Gy and 1 mSv/Gy, approximately one order of magnitude higher than for proton therapy. Although the average secondary doses of IMRT were higher than those of proton therapy for head-and-neck cancers, these differences were not significant. Organ equivalent dose calculations showed that, for prostate cancer patients, the risk of secondary cancers in out-of-field organs, such as the stomach, lungs, and thyroid, was at least 5 times higher for IMRT than for proton therapy, whereas the difference was lower for head-and-neck cancer patients. Conclusions: Comparisons of organ-specific organ equivalent dose showed that the estimated secondary cancer risk using scattering mode in proton therapy is either significantly lower than the cases in IMRT treatment or, at least, does not exceed the risk induced by conventional IMRT treatment.

  8. Empowering Intensity Modulated Proton Therapy Through Physics and Technology: An Overview.

    PubMed

    Mohan, Radhe; Das, Indra J; Ling, Clifton C

    2017-10-01

    Considering the clinical potential of protons attributable to their physical characteristics, interest in proton therapy has increased greatly in this century, as has the number of proton therapy installations. Until recently, passively scattered proton therapy was used almost entirely. Notably, the overall clinical results to date have not shown a convincing benefit of protons over photons. A rapid transition is now occurring with the implementation of the most advanced form of proton therapy, intensity modulated proton therapy (IMPT). IMPT is superior to passively scattered proton therapy and intensity modulated radiation therapy (IMRT) dosimetrically. However, numerous limitations exist in the present IMPT methods. In particular, compared with IMRT, IMPT is highly vulnerable to various uncertainties. In this overview we identify three major areas of current limitations of IMPT: treatment planning, treatment delivery, and motion management, and discuss current and future efforts for improvement. For treatment planning, we need to reduce uncertainties in proton range and in computed dose distributions, improve robust planning and optimization, enhance adaptive treatment planning and delivery, and consider how to exploit the variability in the relative biological effectiveness of protons for clinical benefit. The quality of proton therapy also depends on the characteristics of the IMPT delivery systems and image guidance. Efforts are needed to optimize the beamlet spot size for both improved dose conformality and faster delivery. For the latter, faster energy switching time and increased dose rate are also needed. Real-time in-room volumetric imaging for guiding IMPT is in its early stages with cone beam computed tomography (CT) and CT-on-rails, and continued improvements are anticipated. In addition, imaging of the proton beams themselves, using, for instance, prompt γ emissions, is being developed to determine the proton range and to reduce range uncertainty

  9. Effectiveness of early intensive therapy on β-cell preservation in type 1 diabetes.

    PubMed

    Buckingham, Bruce; Beck, Roy W; Ruedy, Katrina J; Cheng, Peiyao; Kollman, Craig; Weinzimer, Stuart A; DiMeglio, Linda A; Bremer, Andrew A; Slover, Robert; Tamborlane, William V

    2013-12-01

    To assess effectiveness of inpatient hybrid closed-loop control (HCLC) followed by outpatient sensor-augmented pump (SAP) therapy initiated within 7 days of diagnosis of type 1 diabetes on the preservation of β-cell function at 1 year. Sixty-eight individuals (mean age 13.3 ± 5.7 years; 35% female, 92% Caucasian) were randomized to HCLC followed by SAP therapy (intensive group; N = 48) or to the usual-care group treated with multiple daily injections or insulin pump therapy (N = 20). Primary outcome was C-peptide concentrations during mixed-meal tolerance tests at 12 months. Intensive-group participants initiated HCLC a median of 6 days after diagnosis for a median duration of 71.3 h, during which median participant mean glucose concentration was 140 mg/dL (interquartile range 134-153 mg/dL). During outpatient SAP, continuous glucose monitor (CGM) use decreased over time, and at 12 months, only 33% of intensive participants averaged sensor use ≥6 days/week. In the usual-care group, insulin pump and CGM use were initiated prior to 12 months by 15 and 5 participants, respectively. Mean HbA1c levels were similar in both groups throughout the study. At 12 months, the geometric mean (95% CI) of C-peptide area under the curve was 0.43 (0.34-0.52) pmol/mL in the intensive group and 0.52 (0.32-0.75) pmol/mL in the usual-care group (P = 0.49). Thirty-seven (79%) intensive and 16 (80%) usual-care participants had a peak C-peptide concentration ≥0.2 pmol/mL (P = 0.30). In new-onset type 1 diabetes, HCLC followed by SAP therapy did not provide benefit in preserving β-cell function compared with current standards of care.

  10. [The nonlinear relationship between the resuscitation therapy and intensive insulin therapy in severe sepsis and septic shock patients].

    PubMed

    Wang, Da-ming; Zhu, Bin; Ding, Liang-cai; Liu, Ning; Zhang, Jin-song

    2010-06-01

    To study the relationship between the resuscitation therapy and intensive insulin therapy on stress-induced hyperglycemia in severe sepsis and septic shock patients, and to evaluate the value on nonlinear viewpoint in the treatment of patients with sepsis. The data of 129 hospitalized patients with severe sepsis and septic shock were analyzed and they were divided into eight groups every 6 hours in ascending order for full recovery. The resuscitation therapy time of each group was compared with insulin dosage in each unit time with nonlinear least square method. The relationship of the exponential function fit very well between the resuscitation therapy time of each group and the insulin dosage in each unit time. The exponential curve equation was y=e0.739 3-0.015 2x2 (a=0.739 3, b=0.015 2) and the curve fit very well (R2=0.976 943 6). It conforms to the nonlinear viewpoint that the resuscitation therapy time is closely correlated with recovery of dysfunction of endocrine system during the treatment for patients with severe sepsis and septic shock. Therefore, the essence of successful treatment is to concentrate on helping the body rebuild the disorganized network and the recovery of physiological harmony rather than to support and repair the damaged organs.

  11. Corticosteroid treatment and intensive insulin therapy for septic shock in adults: a randomized controlled trial.

    PubMed

    Annane, Djillali; Cariou, Alain; Maxime, Virginie; Azoulay, Elie; D'honneur, Gilles; Timsit, Jean François; Cohen, Yves; Wolf, Michel; Fartoukh, Muriel; Adrie, Christophe; Santré, Charles; Bollaert, Pierre Edouard; Mathonet, Armelle; Amathieu, Roland; Tabah, Alexis; Clec'h, Christophe; Mayaux, Julien; Lejeune, Julie; Chevret, Sylvie

    2010-01-27

    Corticosteroid therapy induces potentially detrimental hyperglycemia in septic shock. In addition, the benefit of adding fludrocortisone in this setting is unclear. To test the efficacy of intensive insulin therapy in patients whose septic shock was treated with hydrocortisone and to assess, as a secondary objective, the benefit of fludrocortisone. A multicenter, 2 x 2 factorial, randomized trial, involving 509 adults with septic shock who presented with multiple organ dysfunction, as defined by a Sequential Organ Failure Assessment score of 8 or more, and who had received hydrocortisone treatment was conducted from January 2006 to January 2009 in 11 intensive care units in France. Patients were randomly assigned to 1 of 4 groups: continuous intravenous insulin infusion with hydrocortisone alone, continuous intravenous insulin infusion with hydrocortisone plus fludrocortisone, conventional insulin therapy with hydrocortisone alone, or conventional insulin therapy with intravenous hydrocortisone plus fludrocortisone. Hydrocortisone was administered in a 50-mg bolus every 6 hours, and fludrocortisone was administered orally in 50-microg tablets once a day, each for 7 days. In-hospital mortality. Of the 255 patients treated with intensive insulin, 117 (45.9%), and 109 of 254 (42.9%) treated with conventional insulin therapy died (relative risk [RR], 1.07; 95% confidence interval [CI], 0.88-1.30; P = .50). Patients treated with intensive insulin experienced significantly more episodes of severe hypoglycemia (<40 mg/dL) than those in the conventional-treatment group, with a difference in mean number of episodes per patient of 0.15 (95% CI, 0.02-0.28; P = .003). At hospital discharge, 105 of 245 patients treated with fludrocortisone (42.9%) died and 121 of 264 (45.8%) in the control group died (RR, 0.94; 95% CI, 0.77-1.14; P = .50). Compared with conventional insulin therapy, intensive insulin therapy did not improve in-hospital mortality among patients who were treated

  12. Lipid-lowering effects of methanolic extract of Vernonia amygdalina leaves in rats fed on high cholesterol diet

    PubMed Central

    Adaramoye, Oluwatosin A; Akintayo, Olajumoke; Achem, Jonah; Fafunso, Michael A

    2008-01-01

    We investigated the lipid-lowering effects of methanolic extract of Vernonia amygdalina (VA) leaves in rats fed an high cholesterol diet, and compared with a standard hypolipidemic drug, Questran (Qu). The effects of VA on the lipid profile were assessed by measuring the levels of total cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, lipid peroxidation (LPO), phospholipid, and glutathione (GSH) in the plasma and liver of the rats. Administration of cholesterol at a dose of 30 mg/0.3 ml, five times in a week for nine consecutive weeks resulted in a significant increase (p < 0.05) in plasma and post mitochondrial fraction (PMF) cholesterol levels by 33% and 55%, respectively. However, treatment with extract of VA at doses of 100 and 200 mg/kg caused a dose dependent reduction in the plasma and PMF cholesterol by 20%, 23% and 23%, 29%, respectively. Similar reduction in cholesterol levels was obtained in Qu-treated rats. Furthermore, VA at 200 mg/kg decreased the plasma and PMF LDL-cholesterol levels by 23% and 49%, and also decreased plasma and PMF triglyceride levels by 29% and 28%, respectively. Also, VA at 100 and 200 mg/kg caused a dose-dependent increase in plasma HDL-cholesterol levels by 41% and 59%, respectively. However, there were no significant differences (p > 0.05) in the PMF HDL-cholesterol and phospholipid levels of the treated rats when compared to hypercholesterolemic rats. There were significant decreases (p < 0.05) in the LPO levels of extract-treated rats. Precisely, VA at 100 and 200 mg/kg decreased the levels of plasma and PMF LPO by 38%, 42% and 35%, 45%, respectively. In addition, VA augmented the cholesterol-induced decrease in PMF glutathione levels of the rats. Taken together, these results suggest the lipid-lowering effects of VA and, probably serve as a new potential natural product for the treatment of hyperlipidemia. PMID:18629374

  13. The Effectiveness of Cervical Spondylosis Therapy with Saunders Traction Device and High-Intensity Laser Therapy: A Randomized Controlled Trial

    PubMed Central

    Haładaj, Robert; Pingot, Mariusz; Topol, Mirosław

    2017-01-01

    Background Among all spinal therapies, treatment of the cervical segment is the most difficult. The cervical segment is particularly sensitive to injuries and pain, and it also requires special care due to its great mobility and most delicate construction. The aim of this research was to evaluate analgesic efficacy and improvement of active mobility of the cervical spine after traction therapy with the Saunders device and high-intensity laser therapy (HILT) immediately after therapy, and in short-, medium-, and long-term follow-up in patients with cervical spondylosis. Material/Methods The study included 174 patients (114 women and 60 men) aged 24–67 years. The patients were divided into two randomized groups. In group I (88 subjects) traction therapy with the Saunders device was applied, and in group II (86 subjects) HILT was applied. The measurement of the range of cervical spine movement, a subjective visual scale for pain (Visual Analog Scale [VAS]), and the Neck Disability Index-Polish Version (NDI) questionnaire were used. Results The results obtained by the Saunders and HILT methods were similar immediately after the therapy and after 4 weeks (the medium-term follow-up). However, in long-term follow-up, there was a significant increase in the maintenance of positive therapeutic effects with the HILT method. Conclusions Both therapeutic methods improved the efficiency and demonstrated analgesic efficacy in patients with cervical spondylosis immediately and in the medium term after the therapy. HILT was more effective than the Saunders method in long-term follow-up. PMID:28104903

  14. Validation of Heart Failure Events in the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) Participants Assigned to Doxazosin and Chlorthalidone

    PubMed Central

    Piller, Linda B; Davis, Barry R; Cutler, Jeffrey A; Cushman, William C; Wright, Jackson T; Williamson, Jeff D; Leenen, Frans HH; Einhorn, Paula T; Randall, Otelio S; Golden, John S; Haywood, L Julian

    2002-01-01

    Background The Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is a randomized, double-blind, active-controlled trial designed to compare the rate of coronary heart disease events in high-risk hypertensive participants initially randomized to a diuretic (chlorthalidone) versus each of three alternative antihypertensive drugs: alpha-adrenergic blocker (doxazosin), ACE-inhibitor (lisinopril), and calcium-channel blocker (amlodipine). Combined cardiovascular disease risk was significantly increased in the doxazosin arm compared to the chlorthalidone arm (RR 1.25; 95% CI, 1.17–1.33; P < .001), with a doubling of heart failure (fatal, hospitalized, or non-hospitalized but treated) (RR 2.04; 95% CI, 1.79–2.32; P < .001). Questions about heart failure diagnostic criteria led to steps to validate these events further. Methods and Results Baseline characteristics (age, race, sex, blood pressure) did not differ significantly between treatment groups (P < .05) for participants with heart failure events. Post-event pharmacologic management was similar in both groups and generally conformed to accepted heart failure therapy. Central review of a small sample of cases showed high adherence to ALLHAT heart failure criteria. Of 105 participants with quantitative ejection fraction measurements provided, (67% by echocardiogram, 31% by catheterization), 29/46 (63%) from the chlorthalidone group and 41/59 (70%) from the doxazosin group were at or below 40%. Two-year heart failure case-fatalities (22% and 19% in the doxazosin and chlorthalidone groups, respectively) were as expected and did not differ significantly (RR 0.96; 95% CI, 0.67–1.38; P = 0.83). Conclusion Results of the validation process supported findings of increased heart failure in the ALLHAT doxazosin treatment arm compared to the chlorthalidone treatment arm. PMID:12459039

  15. A comparison of intensity modulated x-ray therapy to intensity modulated proton therapy for the delivery of non-uniform dose distributions

    NASA Astrophysics Data System (ADS)

    Flynn, Ryan

    2007-12-01

    The distribution of biological characteristics such as clonogen density, proliferation, and hypoxia throughout tumors is generally non-uniform, therefore it follows that the optimal dose prescriptions should also be non-uniform and tumor-specific. Advances in intensity modulated x-ray therapy (IMXT) technology have made the delivery of custom-made non-uniform dose distributions possible in practice. Intensity modulated proton therapy (IMPT) has the potential to deliver non-uniform dose distributions as well, while significantly reducing normal tissue and organ at risk dose relative to IMXT. In this work, a specialized treatment planning system was developed for the purpose of optimizing and comparing biologically based IMXT and IMPT plans. The IMXT systems of step-and-shoot (IMXT-SAS) and helical tomotherapy (IMXT-HT) and the IMPT systems of intensity modulated spot scanning (IMPT-SS) and distal gradient tracking (IMPT-DGT), were simulated. A thorough phantom study was conducted in which several subvolumes, which were contained within a base tumor region, were boosted or avoided with IMXT and IMPT. Different boosting situations were simulated by varying the size, proximity, and the doses prescribed to the subvolumes, and the size of the phantom. IMXT and IMPT were also compared for a whole brain radiation therapy (WBRT) case, in which a brain metastasis was simultaneously boosted and the hippocampus was avoided. Finally, IMXT and IMPT dose distributions were compared for the case of non-uniform dose prescription in a head and neck cancer patient that was based on PET imaging with the Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone (Cu-ATSM) hypoxia marker. The non-uniform dose distributions within the tumor region were comparable for IMXT and IMPT. IMPT, however, was capable of delivering the same non-uniform dose distributions within a tumor using a 180° arc as for a full 360° rotation, which resulted in the reduction of normal tissue integral dose by a factor of

  16. Green Tea as Inhibitor of the Intestinal Absorption of Lipids: Potential Mechanism for its Lipid-Lowering Effect1

    PubMed Central

    Koo, Sung I.; Noh, Sang K.

    2007-01-01

    Animal and epidemiological studies suggest that green tea catechins may reduce the risk of cardiovascular diseases (CHD). The health benefit of green tea has been attributed to its antioxidant and anti-inflammatory properties; however, considerable evidence suggests that green tea and its catechins may reduce the risk of CHD by lowering the plasma levels of cholesterol and triglyceride. Although the mechanism underlying such effect of green tea is yet to be determined, it is evident from in vitro and in vivo studies that green tea or catechins inhibit the intestinal absorption of dietary lipids. Studies in vitro indicate that green tea catechins, particularly EGCG, interfere with the emulsification, digestion, and micellar solubilization of lipids, critical steps involved in the intestinal absorption of dietary fat, cholesterol, and other lipids. Based on the observations, it is likely that green tea or its catechins lower the absorption and tissue accumulation of other lipophilic organic compounds. The available information strongly suggests that green tea or its catechins may be used as safe and effective lipid-lowering therapeutic agents. PMID:17296491

  17. Gemfibrozil, a lipid lowering drug, inhibits the activation of primary human microglia via peroxisome proliferator-activated receptor β

    PubMed Central

    Jana, Malabendu; Pahan, Kalipada

    2012-01-01

    Microglial activation participates in the pathogenesis of various neuroinflammatory and neurodegenerative diseases. However, mechanisms by which microglial activation could be controlled are poorly understood. Peroxisome proliferator-activated receptors (PPAR) are transcription factors belonging to the nuclear receptor super family with diverse effect. This study underlines the importance of PPARβ/δ in mediating the anti-inflammatory effect of gemfibrozil, an FDA-approved lipid-lowering drug, in primary human microglia. Bacterial lipopolysachharides (LPS) induced the expression of various proinflammatory molecules and upregulated the expression of microglial surface marker CD11b in human microglia. However, gemfibrozil markedly suppressed proinflammatory molecules and CD11b in LPS-stimulated microglia. Human microglia expressed PPAR-β and PPAR-γ, but not PPAR-α. Interestingly, either antisense knockdown of PPAR-β or antagonism of PPAR-β by a specific chemical antagonist abrogated gemfibrozil-mediated inhibition of microglial activation. On the other hand, blocking of PPAR-α and PPAR-γ had no effect on gemfibrozil-mediated anti-inflammatory effect in microglia. These results highlight the fact that gemfibrozil regulates microglial activation by inhibiting inflammatory gene expression in a PPAR-β dependent pathway and further reinforce its therapeutic application in several neuroinflammatory and neurodegenerative diseases. PMID:22528839

  18. Green tea as inhibitor of the intestinal absorption of lipids: potential mechanism for its lipid-lowering effect.

    PubMed

    Koo, Sung I; Noh, Sang K

    2007-03-01

    Animal and epidemiological studies suggest that green tea catechins may reduce the risk of cardiovascular diseases [e.g., coronary heart disease (CHD)]. The health benefit of green tea has been attributed to its antioxidant and anti-inflammatory properties; however, considerable evidence suggests that green tea and its catechins may reduce the risk of CHD by lowering the plasma levels of cholesterol and triglyceride. Although the mechanism underlying such effect of green tea is yet to be determined, it is evident from in vitro and in vivo studies that green tea or catechins inhibit the intestinal absorption of dietary lipids. Studies in vitro indicate that green tea catechins, particularly (-)-epigallocatechin gallate, interfere with the emulsification, digestion, and micellar solubilization of lipids, critical steps involved in the intestinal absorption of dietary fat, cholesterol, and other lipids. Based on the observations, it is likely that green tea or its catechins lower the absorption and tissue accumulation of other lipophilic organic compounds. The available information strongly suggests that green tea or its catechins may be used as safe and effective lipid-lowering therapeutic agents.

  19. Intensive non-avoidance group therapy with stutterer adults: preliminary results.

    PubMed

    Georgieva, Dobrinka

    2014-01-01

    The purpose of the present study was to evaluate and document the use and efficacy of intensive non-avoidance group treatment for Bulgarian adults who stutter (AWS), to specify that changes are adopted in different speech situations (in the stabilization phase), and to demonstrate that changes are maintained after intensive therapy. Participants were AWS (n=15, 12 males) with an average age of 25.2 years) Bulgarian native-speakers. Twelve participants were University students and three were clients with tertiary education in different areas. All participants were enrolled in First (overall effect) and Second (interim effect) Stages of Intensive Non-Avoidance Treatment for Stuttering. Van Riper's stuttering modification therapy approach was employed; the latter considers a non-avoidance treatment for stuttering. The treatment was conducted in participants' native Bulgarian language. AWS, as a group (n=15), significantly decreased the number of stuttered utterances after intensive treatment; findings were consistent for participants with moderate as well as severe stuttering. Likewise, there was a significant decrease in duration (in seconds) of disfluencies after treatment; findings were consistent for participants with moderate as well as severe stuttering. Eighty percent of AWS used cancellation immediately and six months after treatment, 65% mastered preparatory sets immediately and six months after treatment, 35% exhibited pull-outs immediately after treatment and 55%, six months post-treatment. These preliminary findings were taken to suggest that intensive non-avoidance treatment for stuttering can be successfully employed with Bulgarian adults who stutter. Special focus was on the positive fluency changes that occurred during the course of therapy regarding the duration of disfluencies in seconds, and index of disfluencies.

  20. Effectiveness of High Intensity Laser Therapy for Reduction of Pain in Knee Osteoarthritis

    PubMed Central

    2016-01-01

    Introduction. Osteoarthritis is the most common type of arthritis. It is the main cause of chronic musculoskeletal pain and disability among the elderly population. Aim. This is a pilot, randomized clinical study about the effect of high intensity laser therapy in patients with osteoarthritis of the knee (OA of the knee). Material and Method. 72 patients (aged between 39 and 83 years) with (clinically and radiographically proved) OA of the knee were included in the study. They were randomized in two groups: therapeutic (test) one (n = 37, 65,11 ± 1,40 (mean ± SD) years old; patients were treated with HILT) and control group (n = 35, 64,71 ± 1,98; patients receive sham laser). Both groups had seven sessions of treatment. VAS and dolorimetry were used for assessment of pain before and after the therapy. Pedobarometric analysis (static and dynamic) was used to assess comparatively the contact surface area and maximum pressure under the heel. Results. Pain levels measured by VAS and dolorimetry decreased significantly in the therapeutic group after seven days of treatment (p< 0,001). Conclusion. The results after seven days of treatment show more intensive and cumulative effect after the application of high intensity laser therapy in comparison to sham laser. This is the reason why HILT can be a method of choice in the treatment of gonarthrosis. PMID:28096711

  1. Hypocaloric Enteral Nutrition Protects Against Hypoglycemia Associated with Intensive Insulin Therapy Better Than Intravenous Dextrose

    PubMed Central

    Kauffmann, Rondi M.; Hayes, Rachel M.; Vanlaeken, Amanda H.; Norris, Patrick R.; Diaz, Jose J.; May, Addison K.; Collier, Bryan R.

    2015-01-01

    Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes. PMID:25347500

  2. Nonlinear 3-D simulation of high-intensity focused ultrasound therapy in the Kidney.

    PubMed

    Suomi, Visa; Jaros, Jiri; Treeby, Bradley; Cleveland, Robin

    2016-08-01

    Kidney cancer is a severe disease which can be treated non-invasively using high-intensity focused ultrasound (HIFU) therapy. However, tissue in front of the transducer and the deep location of kidney can cause significant losses to the efficiency of the treatment. The effect of attenuation, refraction and reflection due to different tissue types on HIFU therapy of the kidney was studied using a nonlinear ultrasound simulation model. The geometry of the tissue was derived from a computed tomography (CT) dataset of a patient which had been segmented for water, bone, soft tissue, fat and kidney. The combined effect of inhomogeneous attenuation and soundspeed was found to result in an 11.0 dB drop in spatial peak-temporal average (SPTA) intensity in the kidney compared to pure water. The simulation without refraction effects showed a 6.3 dB decrease indicating that both attenuation and refraction contribute to the loss in focal intensity. The losses due to reflections at soft tissue interfaces were less than 0.1 dB. Focal point shifting due to refraction effects resulted in -1.3, 2.6 and 1.3 mm displacements in x-, y- and z-directions respectively. Furthermore, focal point splitting into several smaller subvolumes was observed. The total volume of the secondary focal points was approximately 46% of the largest primary focal point. This could potentially lead to undesired heating outside the target location and longer therapy times.

  3. Intensive care nurses' self-reported practice of intravenous fluid bolus therapy.

    PubMed

    Eastwood, Glenn M; Peck, Leah; Young, Helen; Paton, Emily; Glassford, Neil J; Zhang, Ling; Zhu, Guijun; Tanaka, Aiko; Bellomo, Rinaldo

    2015-12-01

    To describe self-reported practice of fluid bolus therapy by intensive care nurses. Multi-choice questionnaire of intensive care nurses conducted in July, 2014. Major university tertiary referral centre. 141 (64%) intensive care nurses responded. The majority of respondents identified 4% albumin as the commonest fluid bolus type and stated a fluid bolus was 250ml; however fluid bolus volume varied from 100ml to 1000ml. Hypotension was identified as the primary physiological trigger for a fluid bolus. In the hour following a fluid bolus for hypotension almost half of respondents expected an 'increase in mean arterial pressure of 0-10mmHg'; for oliguria, >60% expected an 'increase in urinary output of '0.5-1ml/kg/hour'; for low CVP, 50% expected 'an increase in CVP of 3-4mmHg'; and, for tachycardia, 45% expected a 'decrease in heart rate of 11-20beats/minute'. Finally, 7-10% of respondents were 'unsure' about the physiological response to a fluid bolus. Most respondents identified fluid bolus therapy to be at least 250ml of 4% albumin given as quickly as possible; however, volumes from 100 to 1000ml were also accepted. There was much uncertainty about the expected physiological response to fluid bolus therapy according to indication. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Hypocaloric enteral nutrition protects against hypoglycemia associated with intensive insulin therapy better than intravenous dextrose.

    PubMed

    Kauffmann, Rondi M; Hayes, Rachel M; VanLaeken, Amanda H; Norris, Patrick R; Diaz, Jose J; May, Addison K; Collier, Bryan R

    2014-11-01

    Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes.

  5. Bone regeneration by low-level laser therapy and low-intensity pulsed ultrasound therapy in the rabbit calvarium.

    PubMed

    Acar, Ahmet Hüseyin; Yolcu, Ümit; Altındiş, Sedat; Gül, Mehmet; Alan, Hilal; Malkoç, Sıddık

    2016-01-01

    We evaluated the efficacy of low-level laser therapy (LLLT) and low-intensity pulsed ultrasound (LIPUS), alone and in combination, in triggering new bone formation. Sixteen New Zealand white rabbits were given two calvarial defects by using a 6-mm trephine bur, then divided into four treatment groups: control, LLLT, LIPUS, and LLLT+LIPUS. The LLLT and LIPUS groups were treated three times a week for two weeks. The LLLT+LIPUS group received each treatment on the same day, 12h apart, three days a week for two weeks. The animals were sacrificed after three weeks. LLLT and LIPUS, alone and in combination, enhanced new bone formation in comparison to the untreated controls after three weeks (P<0.05); the combined therapy did not produce an additive effect. Our results demonstrate the efficacy of LLLT or LIPUS in triggering bone regeneration. Therapeutic dose and duration requires further study. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Cost considerations for the use of low-air-loss bed therapy in adult intensive care.

    PubMed

    Hibbert, C L; Edbrooke, D L; Corcoran, M; Bright, N N; Kingsley, J N

    1999-06-01

    The aim of this study was to consider the costs of low-air-loss bed therapy in the adult intensive care unit (ICU). A retrospective cost analysis was performed on 269 consecutive patients, 63 of whom had received low-air-loss bed therapy. Patients' APACHE II scores, length of stay (LOS), average daily TISS and ICU outcomes were also collected. Patients' APACHE II and LOS were further studied using odds ratios to test for an association between these factors and likelihood of receiving bed therapy. A prospective 10-week study to identify the amount of nursing time spent repositioning patients was also performed. The results of this study found the bed therapy to represent approximately 3% of the total average cost of care per patient. Patients requiring the bed therapy had higher APACHE II scores on admission, higher average daily TISS points and a longer length of ICU stay. Study of the odds ratios would suggest that the likelihood of patients receiving low-air-loss bed therapy increases if their APACHE II score on admission is between 11 and 20 and they stay > 4.5 days in the ICU. The results of the prospective study found the daily cost of repositioning patients to be 172.80 Pounds per patient.

  7. Proton therapy versus intensity modulated x-ray therapy in the treatment of prostate cancer: Estimating secondary cancer risks

    NASA Astrophysics Data System (ADS)

    Fontenot, Jonas David

    External beam radiation therapy is used to treat nearly half of the more than 200,000 new cases of prostate cancer diagnosed in the United States each year. During a radiation therapy treatment, healthy tissues in the path of the therapeutic beam are exposed to high doses. In addition, the whole body is exposed to a low-dose bath of unwanted scatter radiation from the pelvis and leakage radiation from the treatment unit. As a result, survivors of radiation therapy for prostate cancer face an elevated risk of developing a radiogenic second cancer. Recently, proton therapy has been shown to reduce the dose delivered by the therapeutic beam to normal tissues during treatment compared to intensity modulated x-ray therapy (IMXT, the current standard of care). However, the magnitude of stray radiation doses from proton therapy, and their impact on this incidence of radiogenic second cancers, was not known. The risk of a radiogenic second cancer following proton therapy for prostate cancer relative to IMXT was determined for 3 patients of large, median, and small anatomical stature. Doses delivered to healthy tissues from the therapeutic beam were obtained from treatment planning system calculations. Stray doses from IMXT were taken from the literature, while stray doses from proton therapy were simulated using a Monte Carlo model of a passive scattering treatment unit and an anthropomorphic phantom. Baseline risk models were taken from the Biological Effects of Ionizing Radiation VII report. A sensitivity analysis was conducted to characterize the uncertainty of risk calculations to uncertainties in the risk model, the relative biological effectiveness (RBE) of neutrons for carcinogenesis, and inter-patient anatomical variations. The risk projections revealed that proton therapy carries a lower risk for radiogenic second cancer incidence following prostate irradiation compared to IMXT. The sensitivity analysis revealed that the results of the risk analysis depended only

  8. Intensive sleep deprivation and cognitive behavioral therapy for pharmacotherapy refractory insomnia in a hospitalized patient.

    PubMed

    Breitstein, Joshua; Penix, Brandon; Roth, Bernard J; Baxter, Tristin; Mysliwiec, Vincent

    2014-06-15

    The case of a 59-year-old woman psychiatrically hospitalized with comorbid insomnia, suicidal ideation, and generalized anxiety disorder is presented. Pharmacologic therapies were unsuccessful for treating insomnia prior to and during hospitalization. Intensive sleep deprivation was initiated for 40 consecutive hours followed by a recovery sleep period of 8 hours. Traditional components of cognitive behavioral therapy for insomnia (CBTi), sleep restriction, and stimulus control therapies, were initiated on the ward. After two consecutive nights with improved sleep, anxiety, and absence of suicidal ideation, the patient was discharged. She was followed in the sleep clinic for two months engaging in CBTi. Treatment resulted in substantial improvement in her insomnia, daytime sleepiness, and anxiety about sleep. Sleep deprivation regimens followed by a restricted sleep recovery period have shown antidepressant effects in depressed patients. Similar treatment protocols have not been investigated in patients with pharmacotherapy refractory insomnia and generalized anxiety disorder.

  9. Physical therapy observation and assessment in the neonatal intensive care unit.

    PubMed

    Byrne, Eilish; Campbell, Suzann K

    2013-02-01

    This article presents the elements of the Observation and Assessment section of the Infant Care Path for Physical Therapy in the Neonatal Intensive Care Unit (NICU). The types of physical therapy assessments presented in this path are evidence-based and the suggested timing of these assessments is primarily based on practice knowledge from expert therapists, with supporting evidence cited. Assessment in the NICU begins with a thorough review of the health care record. Assessment proceeds by using the least invasive methods of gathering the behavioral, developmental, physiologic, and musculoskeletal information needed to implement a physical therapy plan of care. As the neonate matures and can better tolerate handling, assessment methods include lengthier standardized tests with the psychometric properties needed for informing diagnosis and intervention planning. Standardized tests and measures for screening, diagnosis, and developmental assessment are appraised and special considerations for assessment of neonates in the NICU are discussed.

  10. [Long-term intermittent renal replacement therapy at an intensive care unit].

    PubMed

    Bellomo, R; Baldwin, I; Toshio, N; Wan, L; Fealy, N; Ronco, C

    2005-01-01

    Standard intermittent hemodialysis (IHD) used for the treatment of acute renal failure (ARF) at an intensive care unit has significant biochemical and physiological drawbacks. In the past 20 years, these drawbacks have stimulated the development of continuous renal replacement therapy (CRRT) and its ever-increasing use. However, CRRT is technically complicated and requires 24-hour monitoring. In some clinics, the use of CRRT leads to that each patient is under his/her nurse's surveillance, instead 1 nurse per 2 patients as before; this change has economic consequences and may limit nursing accessibility to other patients. The procedures prolonging intermittent therapy do not require 24-hour monitoring may benefit the treatment of ARF at the intensive care therapy. In this paper the authors call such procedures for continuous intermittent renal replacement therapy. They are characterized by a number of basic principles: (1) the use of modified or standard dialysis apparatuses; (2) the application of diffuse, convection, or both; (3) a certain reduction in the rate of elimination of dissolved substances as compared with IHD; (4) more prolonged treatment: above usual 3 or 4 hours of IHD, but not more than 8-12 hours (hence the term "intermittent"); (5) the use of on-line generation dialysate or substituting fluid. Information on the effectiveness and safety of this procedure is being now compiled.

  11. Intensive Sleep Deprivation and Cognitive Behavioral Therapy for Pharmacotherapy Refractory Insomnia in a Hospitalized Patient

    PubMed Central

    Breitstein, Joshua; Penix, Brandon; Roth, Bernard J.; Baxter, Tristin; Mysliwiec, Vincent

    2014-01-01

    The case of a 59-year-old woman psychiatrically hospitalized with comorbid insomnia, suicidal ideation, and generalized anxiety disorder is presented. Pharmacologic therapies were unsuccessful for treating insomnia prior to and during hospitalization. Intensive sleep deprivation was initiated for 40 consecutive hours followed by a recovery sleep period of 8 hours. Traditional components of cognitive behavioral therapy for insomnia (CBTi), sleep restriction, and stimulus control therapies, were initiated on the ward. After two consecutive nights with improved sleep, anxiety, and absence of suicidal ideation, the patient was discharged. She was followed in the sleep clinic for two months engaging in CBTi. Treatment resulted in substantial improvement in her insomnia, daytime sleepiness, and anxiety about sleep. Sleep deprivation regimens followed by a restricted sleep recovery period have shown antidepressant effects in depressed patients. Similar treatment protocols have not been investigated in patients with pharmacotherapy refractory insomnia and generalized anxiety disorder. Citation: Breitstein J, Penix B, Roth BJ, Baxter T, Mysliwiec V. Intensive sleep deprivation and cognitive behavioral therapy for pharmacotherapy refractory insomnia in a hospitalized patient. J Clin Sleep Med 2014;10(6):689-690. PMID:24932151

  12. Intensive care physicians' attitudes and perceptions on nutrition therapy: a web-based survey.

    PubMed

    Cunha, Haroldo Falcão Ramos da; Salluh, Jorge Ibrain Figueira; França, Maria de Fátima

    2010-03-01

    Nutritional therapy is an important element in critical ill patient care. Although recognized as specialty, multidisciplinary teams in nutrition support are scarce in our country. Possibly, nutrition support therapy is applied by intensive care physicians and this may vary. The aim of the study is describe these specialists perceptions about theirs attitudes in enteral nutrition support. A questionnaire was elaborated in an on-line platform. After pre-validation, it was sent by electronic mail to intensivists. In 30 days answers were collected, considering only the full-filled questionnaires. One hundred an fourteen forms were returned, 112 were analyzed. The responders were localized at majority in southeastern region. About beggining of nutritional support, the majority of answers reflect perceptions in accord to specialists societies recommendations. The responders' perception the frequent utilization of assistentials protocols in nutrition care. After support beginning, the responders perceptions about theirs participation in changes in therapeutic plan seems to be lower. The self-knowledge about the theme among the responders was 6.0 (arithmetic media) in a 1 to 10 scale. More studies are necessary to evaluate nutritional support practices among intensive care physicians. Alternatives to on-line platform should be considered. Possibly, intensive care physicians do better in the initial phases of enteral support than in continuity of care. Intensive care physicians knowledge about the issue is suboptimal.

  13. Constraint therapy versus intensive training: implications for motor control and brain plasticity after stroke.

    PubMed

    Medée, Béatrice; Bellaiche, Soline; Revol, Patrice; Jacquin-Courtois, Sophie; Arsenault, Lisette; Guichard-Mayel, Audrey; Delporte, Ludovic; Rode, Gilles; Rossetti, Yves; Boisson, Dominique; Luauté, Jacques

    2010-12-01

    Many studies have demonstrated that constraint induced movement therapy (CIMT) improves upper limb motor impairment following stroke. This rehabilitation method combines constraint of the less-affected upperlimb with intensive training of the paretic limb. The aim of the present study was to evaluate, in a single case study, the respective effects of each of these two therapeutic interventions. The patient selected was a 32-year-old right-handed woman. Three and a half years prior to inclusion, she suffered a left capsular infarct responsible for a right hemiparesis. Several assessments were carried out before and after constraint therapy and then after intensive training. Each assessment included measures of hand function as well as a three-dimensional (3D) analysis of prehension. Results showed a significant improvement of motor performance after the constraint period and an additional amelioration after the intensive training period. Kinematic analysis showed that the transport phase of movement (movement time and velocity peaks) was improved after the constraint period, whereas the grasping phase (maximum grip aperture) was modified after intensive training. These data could reflect a specific effect of treatment on each phase of the prehension task, or a more general proximal-to-distal gradient of recovery. Although firm conclusions are not warranted on the basis of this single case study, we confirm the utility of 3D motion analysis to evaluate objectively the effectiveness of a therapeutic intervention. We also discuss the implications of our findings for understanding processes of motor control reorganisation.

  14. Incorporating deliverable monitor unit constraints into spot intensity optimization in intensity-modulated proton therapy treatment planning

    NASA Astrophysics Data System (ADS)

    Cao, Wenhua; Lim, Gino; Li, Xiaoqiang; Li, Yupeng; Zhu, X. Ronald; Zhang, Xiaodong

    2013-08-01

    The purpose of this study is to investigate the feasibility and impact of incorporating deliverable monitor unit (MU) constraints into spot intensity optimization (SIO) in intensity-modulated proton therapy (IMPT) treatment planning. The current treatment planning system (TPS) for IMPT disregards deliverable MU constraints in the SIO routine. It performs a post-processing procedure on an optimized plan to enforce deliverable MU values that are required by the spot scanning proton delivery system. This procedure can create a significant dose distribution deviation between the optimized and post-processed deliverable plans, especially when small spot spacings are used. In this study, we introduce a two-stage linear programming approach to optimize spot intensities and constrain deliverable MU values simultaneously, i.e., a deliverable SIO (DSIO) model. Thus, the post-processing procedure is eliminated and the associated optimized plan deterioration can be avoided. Four prostate cancer cases at our institution were selected for study and two parallel opposed beam angles were planned for all cases. A quadratic programming based model without MU constraints, i.e., a conventional SIO (CSIO) model, was also implemented to emulate commercial TPS. Plans optimized by both the DSIO and CSIO models were evaluated for five different settings of spot spacing from 3 to 7 mm. For all spot spacings, the DSIO-optimized plans yielded better uniformity for the target dose coverage and critical structure sparing than did the CSIO-optimized plans. With reduced spot spacings, more significant improvements in target dose uniformity and critical structure sparing were observed in the DSIO than in the CSIO-optimized plans. Additionally, better sparing of the rectum and bladder was achieved when reduced spacings were used for the DSIO-optimized plans. The proposed DSIO approach ensures the deliverability of optimized IMPT plans that take into account MU constraints. This eliminates the post

  15. Occupational therapy, physical therapy and speech-language pathology in the neonatal intensive care unit: Patterns of therapy usage in a level IV NICU.

    PubMed

    Ross, Katherine; Heiny, Elizabeth; Conner, Sandra; Spener, Patricia; Pineda, Roberta

    2017-05-01

    1) To describe the use of occupational therapy (OT), physical therapy (PT) and speech-language pathology (SLP) services in a level IV neonatal intensive care unit (NICU), 2) to describe predictors of early therapy usage, and 3) to test the hypothesis that more NICU-based therapy will relate to better neurobehavioral outcomes. Seventy-nine infants born ≤32 weeks gestation had therapy interventions, as standard of care, tracked across NICU hospitalization. Infants received neurobehavioral testing prior to NICU discharge. All (100%) received OT and PT, and 41 (51%) received SLP. The average age at initiation of OT, PT, and SLP was 30.4±1.4, 30.3±1.4, and 35.9±2.3 weeks postmenstrual age, respectively. Infants received therapy an average of 1.8±.4, 1.8±.4 and 1.1±.5 times per week for OT, PT and SLP, respectively. There were 56 different therapeutic interventions performed. There was overlap in the interventions provided by different NICU therapists; however, interventions unique to each discipline were identified. More therapy was not related to better neurobehavioral outcomes, but rather more frequent therapy could be attributed to more complex medical conditions (p<0.05). Early therapy services in the NICU can start early in gestation and continue routinely until NICU discharge in order to optimize outcomes. These findings can aid our understanding of how neonatal therapy services are implemented in a level IV NICU. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The long term effectiveness of intensive stuttering therapy: a mixed methods study.

    PubMed

    Irani, Farzan; Gabel, Rodney; Daniels, Derek; Hughes, Stephanie

    2012-09-01

    The purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. The study used a mixed methods design. The core method was a phenomenological approach using semi-structured interviews. Objective clinical data was gathered concurrently. This included archival records and current measures on a variety of assessments to evaluate stuttering severity and attitudes toward communication. The major themes generated from participants' transcripts included (1) the positive effects of the Duration and Nature of the Program; (2) Speech Techniques Learned; (3) Attitude Change and Counseling; and (4) activities related to Desensitization and Transfer. The participants also reported positive effects of their personal motivation and clinician attitudes. Clinical data indicated that the participants made measurable clinical gains on all measures of stuttering severity and attitude change following the intensive clinic and these changes were maintained long after the program was completed. It appears that this intensive stuttering therapy program is effective for making positive changes in behavioral measures of speech disfluencies, and attitudes. Clients reported multiple factors directly related to the program and personal factors that contributed to treatment effectiveness. Hence, future studies should explore and report on a variety of factors related to communication attitudes and overall quality of life in addition to behavioral measures of speech. After reading this article, the learner will be able to: (a) identify the basic tenets of evidence-based practice; (b) summarize what we currently know about the effectiveness of behavioral treatments of stuttering; (c) identify factors that client report as important to

  17. Clinical outcomes of intensity-modulated pelvic radiation therapy for carcinoma of the cervix.

    PubMed

    Hasselle, Michael D; Rose, Brent S; Kochanski, Joel D; Nath, Sameer K; Bafana, Rounak; Yashar, Catheryn M; Hasan, Yasmin; Roeske, John C; Mundt, Arno J; Mell, Loren K

    2011-08-01

    To evaluate disease outcomes and toxicity in cervical cancer patients treated with pelvic intensity-modulated radiation therapy (IMRT). We included all patients with Stage I-IVA cervical carcinoma treated with IMRT at three different institutions from 2000-2007. Patients treated with extended field or conventional techniques were excluded. Intensity-modulated radiation therapy plans were designed to deliver 45 Gy in 1.8-Gy daily fractions to the planning target volume while minimizing dose to the bowel, bladder, and rectum. Toxicity was graded according to the Radiation Therapy Oncology Group system. Overall survival and disease-free survival were estimated by use of the Kaplan-Meier method. Pelvic failure, distant failure, and late toxicity were estimated by use of cumulative incidence functions. The study included 111 patients. Of these, 22 were treated with postoperative IMRT, 8 with IMRT followed by intracavitary brachytherapy and adjuvant hysterectomy, and 81 with IMRT followed by planned intracavitary brachytherapy. Of the patients, 63 had Stage I-IIA disease and 48 had Stage IIB-IVA disease. The median follow-up time was 27 months. The 3-year overall survival rate and the disease-free survival rate were 78% (95% confidence interval [CI], 68-88%) and 69% (95% CI, 59-81%), respectively. The 3-year pelvic failure rate and the distant failure rate were 14% (95% CI, 6-22%) and 17% (95% CI, 8-25%), respectively. Estimates of acute and late Grade 3 toxicity or higher were 2% (95% CI, 0-7%) and 7% (95% CI, 2-13%), respectively. Intensity-modulated radiation therapy is associated with low toxicity and favorable outcomes, supporting its safety and efficacy for cervical cancer. Prospective clinical trials are needed to evaluate the comparative efficacy of IMRT vs. conventional techniques. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Clinical Outcomes of Intensity-Modulated Pelvic Radiation Therapy for Carcinoma of the Cervix

    SciTech Connect

    Hasselle, Michael D.; Rose, Brent S.; Kochanski, Joel D.; Nath, Sameer K.; Bafana, Rounak; Yashar, Catheryn M.; Hasan, Yasmin; Roeske, John C.; Mundt, Arno J.; Mell, Loren K.

    2011-08-01

    Purpose: To evaluate disease outcomes and toxicity in cervical cancer patients treated with pelvic intensity-modulated radiation therapy (IMRT). Methods and Materials: We included all patients with Stage I-IVA cervical carcinoma treated with IMRT at three different institutions from 2000-2007. Patients treated with extended field or conventional techniques were excluded. Intensity-modulated radiation therapy plans were designed to deliver 45 Gy in 1.8-Gy daily fractions to the planning target volume while minimizing dose to the bowel, bladder, and rectum. Toxicity was graded according to the Radiation Therapy Oncology Group system. Overall survival and disease-free survival were estimated by use of the Kaplan-Meier method. Pelvic failure, distant failure, and late toxicity were estimated by use of cumulative incidence functions. Results: The study included 111 patients. Of these, 22 were treated with postoperative IMRT, 8 with IMRT followed by intracavitary brachytherapy and adjuvant hysterectomy, and 81 with IMRT followed by planned intracavitary brachytherapy. Of the patients, 63 had Stage I-IIA disease and 48 had Stage IIB-IVA disease. The median follow-up time was 27 months. The 3-year overall survival rate and the disease-free survival rate were 78% (95% confidence interval [CI], 68-88%) and 69% (95% CI, 59-81%), respectively. The 3-year pelvic failure rate and the distant failure rate were 14% (95% CI, 6-22%) and 17% (95% CI, 8-25%), respectively. Estimates of acute and late Grade 3 toxicity or higher were 2% (95% CI, 0-7%) and 7% (95% CI, 2-13%), respectively. Conclusions: Intensity-modulated radiation therapy is associated with low toxicity and favorable outcomes, supporting its safety and efficacy for cervical cancer. Prospective clinical trials are needed to evaluate the comparative efficacy of IMRT vs. conventional techniques.

  19. Treatment planning, optimization, and beam delivery technqiues for intensity modulated proton therapy

    NASA Astrophysics Data System (ADS)

    Sengbusch, Evan R.

    , beamlet weight, the number of delivered beamlets, and the number of delivery angles. These methods are evaluated via treatment planning studies including left-sided whole breast irradiation, lung stereotactic body radiotherapy, nasopharyngeal carcinoma, and whole brain radiotherapy with hippocampal avoidance. Improvements in efficiency and efficacy relative to traditional proton therapy and intensity modulated photon radiation therapy are discussed.

  20. Implementation of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit.

    PubMed

    Lavrentieva, A; Kontou, P; Soulountsi, V; Kioumis, J; Chrysou, O; Bitzani, M

    2015-09-30

    The purpose of this study was to examine the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in burn patients with infectious complications. All burn patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections were eligible. Patients were assigned to either a procalcitonin-guided (study group) or a standard (control group) antibiotic regimen. The following variables were analyzed and compared in both groups: duration of antibiotic treatment, mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score (days 1-28), length of ICU and hospital stay. A total of 46 Burn ICU patients receiving antibiotic therapy were enrolled in this study. In 24 patients antibiotic therapy was guided by daily procalcitonin and clinical assessment. PCT guidance resulted in a smaller antibiotic exposure (10.1±4 vs. 15.3±8 days, p=0.034) without negative effects on clinical outcome characteristics such as mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score, length of ICU and hospital stay. The findings thus show that use of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit may contribute to the reduction of antibiotic exposure without compromising clinical outcome parameters.

  1. Implementation of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit

    PubMed Central

    Lavrentieva, A.; Kontou, P.; Soulountsi, V.; Kioumis, J.; Chrysou, O.; Bitzani, M.

    2015-01-01

    Summary The purpose of this study was to examine the hypothesis that an algorithm based on serial measurements of procalcitonin (PCT) allows reduction in the duration of antibiotic therapy compared with empirical rules, and does not result in more adverse outcomes in burn patients with infectious complications. All burn patients requiring antibiotic therapy based on confirmed or highly suspected bacterial infections were eligible. Patients were assigned to either a procalcitonin-guided (study group) or a standard (control group) antibiotic regimen. The following variables were analyzed and compared in both groups: duration of antibiotic treatment, mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score (days 1-28), length of ICU and hospital stay. A total of 46 Burn ICU patients receiving antibiotic therapy were enrolled in this study. In 24 patients antibiotic therapy was guided by daily procalcitonin and clinical assessment. PCT guidance resulted in a smaller antibiotic exposure (10.1±4 vs. 15.3±8 days, p=0.034) without negative effects on clinical outcome characteristics such as mortality rate, percentage of patients with relapse or superinfection, maximum SOFA score, length of ICU and hospital stay. The findings thus show that use of a procalcitonin-guided algorithm for antibiotic therapy in the burn intensive care unit may contribute to the reduction of antibiotic exposure without compromising clinical outcome parameters. PMID:27279801

  2. [Prognosis improvements in children with acute myelocytic leucemia after more intensive induction therapy (author's transl)].

    PubMed

    Scheer, U; Schellong, G; Riehm, H

    1979-03-01

    Between October 1974 and October 1978 23 children with acute myelocytic leucemia (AML) received intensive therapy in the Univ.-Kinderklinik Münster: 4 children were treated according to the ALGB-protocol consisting of 5-7 day courses of ARA-C-infusion and 3 DNR-injections. 19 patients received the West-Berlin-protocol: The first 7 the original ALL protocol, 11 the modified form of AML, which will be presented here as AML-therapy-study BFM 78. 4 of the 23 patients died with early acute cerebral bleeding. 2 patients were nonresponders. 17 children went into remission. One girl died in remission of septicemic aspergillosis. 4 children had a relapse. In November 1978 there were still 12 patients in continuous complete remission, 3 of them already without therapy. 13 of the 19 patients, who were treated with the West-Berlin-protocol went into remission. 1 had a relapse. At present there are 11 patients in continuous complete remission. The above results and those found in the literature could signify that the long term prognosis of children with AML will be improved. To coordinate efforts toward this goal a cooperative AML-therapy-study in the "Deutsche Arbeitsgemeinschaft für Leukämieforschung" (BFM-group) using the here presented therapy protocol was formed in November 1978.

  3. Impact of vision impairment on intensity of occupational therapy utilization and outcomes in subacute rehabilitation.

    PubMed

    Cimarolli, Verena R; Morse, Alan R; Horowitz, Amy; Reinhardt, Joann P

    2012-01-01

    To examine whether vision impairment is a predictor of intensity of occupational therapy utilization and outcomes in a sample of older adults ages ≥55 receiving subacute rehabilitation in a long-term care setting. Data for this cohort study were collected by means of structured, in-person interviews with 100 older adult rehabilitation patients at admission to a subacute unit in a long-term care facility and by medical chart review after discharge. Regression analyses indicated that after controlling for sociodemographic, health, and social support variables, worse contrast sensitivity was a significant predictor of decreased time in occupational therapy, and worse visual acuity was a significant predictor of higher functional dependency at discharge. Vision impairment may prevent full use of occupational therapy and hinder occupational therapy efficacy in subacute care settings. Study findings underscore the importance of developing low vision rehabilitation interventions that can be delivered in conjunction with more traditional subacute rehabilitation. Copyright © 2012 by the American Occupational Therapy Association, Inc.

  4. Rare PPARA variants and extreme response to fenofibrate in the Genetics of Lipid Lowering Drugs and Diet Network Study

    PubMed Central

    Irvin, Marguerite R; Zhang, Qunyuan; Kabagambe, Edmond K; Perry, Rodney T; Straka, Robert J.; Tiwari, Hemant K; Borecki, Ingrid B; Shimmin, Lawrence C.; Stuart, Colin; Zhong, Yu; Hixson, James E; Arnett, Donna K

    2012-01-01

    Objective Fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, reduces triglyceride (TG) concentrations by 25–60%. Given significant inter-individual variation in TG response, we investigated the association of PPARA rare variants with treatment response in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Methods We calculated change in TG concentration (ΔTG) among 861 GOLDN participants treated with fenofibrate (160 mg/day) for 3 weeks. From the distribution of ΔTG adjusted for age and sex, the 150 highest and 150 lowest fenofibrate responders were selected from the tails of the distribution for PPARA resequencing. The resequencing strategy was based on VariantSEQrtm technology for the amplification of exons and regulatory regions. Results We identified 73 variants with an average minor allele frequency (MAF) of 4.8% (range 0.2%–16%). We tested the association of rare variants located in a coding or regulatory region (MAF<1%, 13 variants) with treatment response group via an indicator variable (presence/absence of ≥1 rare variant) using general linear mixed models to allow for adjustment for family relationship. After adjusting for baseline fasting TG concentration carrying at least one rare variant was associated with low fenofibrate response (odds ratio=6.46; 95% CI 1.4–30.8). Carrier status was also associated with relative change in total cholesterol concentration (P=0.02), but not high density lipoprotein or low density lipoprotein concentration. Conclusions Rare, potentially functional variants in PPARA may play a role in TG response to fenofibrate, but future experimental studies will be necessary to replicate the findings and confirm functional effects. PMID:22336959

  5. Gemfibrozil, a Lipid-lowering Drug, Increases Myelin Genes in Human Oligodendrocytes via Peroxisome Proliferator-activated Receptor-β*

    PubMed Central

    Jana, Malabendu; Mondal, Susanta; Gonzalez, Frank J.; Pahan, Kalipada

    2012-01-01

    An increase in CNS remyelination and a decrease in CNS inflammation are important steps to halt the progression of multiple sclerosis. Earlier studies have shown that gemfibrozil, a lipid-lowering drug, has anti-inflammatory properties. The current study identified another novel property of gemfibrozil in stimulating the expression of myelin-specific genes (myelin basic protein, myelin oligodendrocyte glycoprotein, 2′,3′-cyclic-nucleotide 3′-phosphodiesterase, and proteolipid protein (PLP)) in primary human oligodendrocytes, mixed glial cells, and spinal cord organotypic cultures. Although gemfibrozil is a known activator of peroxisome proliferator-activated receptor-α (PPAR-α), we were unable to detect PPAR-α in either gemfibrozil-treated or untreated human oligodendrocytes, and gemfibrozil increased the expression of myelin genes in oligodendrocytes isolated from both wild type and PPAR-α(−/−) mice. On the other hand, gemfibrozil markedly increased the expression of PPAR-β but not PPAR-γ. Consistently, antisense knockdown of PPAR-β, but not PPAR-γ, abrogated the stimulatory effect of gemfibrozil on myelin genes in human oligodendrocytes. Gemfibrozil also did not up-regulate myelin genes in oligodendroglia isolated from PPAR-β(−/−) mice. Chromatin immunoprecipitation analysis showed that gemfibrozil induced the recruitment of PPAR-β to the promoter of PLP and myelin oligodendrocyte glycoprotein genes in human oligodendrocytes. Furthermore, gemfibrozil treatment also led to the recruitment of PPAR-β to the PLP promoter in vivo in the spinal cord of experimental autoimmune encephalomyelitis mice and suppression of experimental autoimmune encephalomyelitis symptoms in PLP-T cell receptor transgenic mice. These results suggest that gemfibrozil stimulates the expression of myelin genes via PPAR-β and that gemfibrozil, a prescribed drug for humans, may find further therapeutic use in demyelinating diseases. PMID:22879602

  6. Epigenome-Wide Association Study of Fasting Blood Lipids in the Genetics of Lipid Lowering Drugs and Diet Network Study

    PubMed Central

    Irvin, Marguerite R.; Zhi, Degui; Joehanes, Roby; Mendelson, Michael; Aslibekyan, Stella; Claas, Steven A.; Thibeault, Krista S.; Patel, Nikita; Day, Kenneth; Jones, Lindsay Waite; Liang, Liming; Chen, Brian H.; Yao, Chen; Tiwari, Hemant K.; Ordovas, Jose M.; Levy, Daniel; Absher, Devin; Arnett, Donna K.

    2014-01-01

    Background Genetic research regarding blood lipids has largely focused on DNA sequence variation; few studies have explored epigenetic effects. Genome-wide surveys of DNA methylation may uncover epigenetic factors influencing lipid metabolism. Methods and Results To identify whether differential methylation of cytosine-guanine dinucleotides (CpGs) correlated with lipid phenotypes, we isolated DNA from CD4+ T-cells and quantified proportion of sample methylation at over 450,000 CpGs using the Illumina Infinium HumanMethylation450 Beadchip in 991 participants of the Genetics of Lipid Lowering Drugs and Diet Network. We modeled percent methylation at individual CpGs as a function of fasting very low density lipoprotein cholesterol (VLDL-C) and triglycerides (TG) using mixed linear regression adjusted for age, gender, study site, cell purity, and family structure. Four CpGs (cg00574958, cg17058475, cg01082498, cg09737197) in intron 1 of carnitine palmitoyltransferase 1A (CPT1A) were strongly associated with VLDL-C (P=1.8*10-21 to 1.6*10-8) and TG (P=1.6*10-26 to 1.5*10-9). Array findings were validated by bisulfite sequencing. We performed qPCR experiments demonstrating that methylation of the top CpG (cg00574958) was correlated with CPT1A expression. The association of cg00574958 with TG and CPT1A expression were replicated in the Framingham Heart Study (P=4.1*10-14 and 3.1*10-13, respectively). DNA methylation at CPT1A cg00574958 explained 11.6% and 5.5% of the variation in TG in the discovery and replication cohorts, respectively. Conclusions This genome-wide epigenomic study identified CPT1A methylation as strongly and robustly associated with fasting VLDL-C and TG. Identifying novel epigenetic contributions to lipid traits may inform future efforts to identify new treatment targets and/or biomarkers of disease risk. PMID:24920721

  7. Consumer’s Perception on Design and Layout of Consumer Medical Information Leaflets on Obesity and Lipid Lowering Drugs

    PubMed Central

    Mathew, Elizabeth M.; Rajiah, Kingston; Sharma, Krishana Kumar

    2013-01-01

    Background: Printed education materials are often used to augment healthcare professional’s verbal information to consumers so it serves as an important component of symptom management. They also enhance the teaching process and can be used by consumers as a home reference. Objective: This study was aimed to interpret consumers’ perception on Consumer Medical Information Leaflets (CMILs) on obesity and lipid lowering drugs, on design and layout using the standard method such as Baker Able Leaflet Design (BALD). Material and Methods: Convenience sampling was done. The study was conducted over a period of 3 years in community pharmacy settings in Tamil Nadu, India. The Consumer Medical Information Leaflets (CMILs) were randomly collected from different community pharmacies. Total of 19 CMILs which are commonly used by the consumers were collected and CMILs were assessed using BALD assessment tool Results: According to BALD assessment (46.28%) leaflets were rated as ‘above standard’ and (53.72) leaflets were rated as ‘standard or poor’ in layout and design since their scores were less than 25. This shows that this issue may be important from the patient’s perspective, which may discourage patient from actually reading the CMILs. Conclusion: In India, generally CMILs are continued to be prepared in English and with higher proportion of consumers with English illiteracy. CMILs, which are prepared without taking consideration of reading level of consumers and proper layout and design, may not achieve the intended purpose. This is an important aspect that any company has to reckon while preparing leaflets and at least in some major local languages in which CMILs have to be prepared. PMID:24551641

  8. Metabolomic and pharmacokinetic study on the mechanism underlying the lipid-lowering effect of oral-administrated berberine

    PubMed Central

    Gu, Shenghua; Cao, Bei; Sun, Runbin; Tang, Yueqing; Paletta, Janice L.; Wu, Xiao-Lei; Liu, Linsheng; Zha, Weibin; Zhao, Chunyan; Li, Yan; Radlon, Jason M.; Hylemon, Phillip B.; Zhou, Huiping; Aa, Jiye; Wang, Guangji

    2014-01-01

    Clinic and animal studies demonstrated that oral-administrated berberine had distinct lipid-lowering effect. However, pharmacokinetic studies showed berberine was poorly absorbed into the body so that the levels of berberine in the blood and target tissues were far below the effective concentrations revealed. To probe the underlying mechanism, the effect of berberine on biological system was studied on a high-fat-diet-induced hamster hyperlipidemia model. Our results showed that intragastric-administered berberine was poorly absorbed into circulation and most berberine accumulated in gut content. Although the bioavailability for intragastric-administered berberine was much lower than that of intraperitoneal-administered berberine, it had stronger lipid-lowing effect, indicating gastrointestinal is a potential target for hypolipidemic effect of berberine. Metabolomic study on both serum and gut content showed that oral-administrated berberine significantly regulated molecules involved in lipid metabolism, and increased the generation of bile acids in the hyperlipidemic model. DNA analysis revealed that the oral-administered berberine modulated the gut microbiota, and BBR showed a significant inhibition on the 7α-dehydroxylation conversion of cholic acid to deoxycholic acid, indicating a decreased elimination of bile acids in the gut. However, in model hamsters, elevated bile acids failed to down-regulate the expression and function of CYP7A1 in a negative feed-back way. It was suggested that the hypocholesterolemic effect for oral-administrated berberine is involved in its effect on modulating the turnover of bile acids and farnesoid X receptor signal pathway. PMID:25411028

  9. Mortality and morbidity during and after Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial: results by sex.

    PubMed

    Oparil, Suzanne; Davis, Barry R; Cushman, William C; Ford, Charles E; Furberg, Curt D; Habib, Gabriel B; Haywood, L Julian; Margolis, Karen; Probstfield, Jeffrey L; Whelton, Paul K; Wright, Jackson T

    2013-05-01

    To determine whether an angiotensin-converting enzyme inhibitor (lisinopril) or calcium channel blocker (amlodipine) is superior to a diuretic (chlorthalidone) in reducing cardiovascular disease incidence in sex subgroups, we carried out a prespecified subgroup analysis of 15 638 women and 17 719 men in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Total follow-up (active treatment + passive surveillance using national administrative databases to ascertain deaths and hospitalizations) was 8 to 13 years. The primary outcome was fatal coronary heart disease or nonfatal myocardial infarction. Secondary outcomes included all-cause mortality, stroke, combined cardiovascular disease (coronary heart disease death, nonfatal myocardial infarction, stroke, angina, coronary revascularization, heart failure [HF], or peripheral vascular disease), and end-stage renal disease. In-trial rates of HF, stroke, and combined cardiovascular disease were significantly higher for lisinopril compared with chlorthalidone, and rates of HF were significantly higher for amlodipine compared with chlorthalidone in both men and women. There were no significant treatment sex interactions. These findings did not persist through the extension period with the exception of the HF result for amlodipine versus chlorthalidone, which did not differ significantly by sex. For both women and men, rates were not lower in the amlodipine or lisinopril groups than in the chlorthalidone group for either the primary coronary heart disease outcome or any other cardiovascular disease outcome, and chlorthalidone-based treatment resulted in the lowest risk of HF. Neither lisinopril nor amlodipine is superior to chlorthalidone for initial treatment of hypertension in either women or men. Clinical Trial Registration- clinicaltrials.gov; Identifier: NCT00000542.

  10. A modular approach to intensity-modulated arc therapy optimization with noncoplanar trajectories

    NASA Astrophysics Data System (ADS)

    Papp, Dávid; Bortfeld, Thomas; Unkelbach, Jan

    2015-07-01

    Utilizing noncoplanar beam angles in volumetric modulated arc therapy (VMAT) has the potential to combine the benefits of arc therapy, such as short treatment times, with the benefits of noncoplanar intensity modulated radiotherapy (IMRT) plans, such as improved organ sparing. Recently, vendors introduced treatment machines that allow for simultaneous couch and gantry motion during beam delivery to make noncoplanar VMAT treatments possible. Our aim is to provide a reliable optimization method for noncoplanar isocentric arc therapy plan optimization. The proposed solution is modular in the sense that it can incorporate different existing beam angle selection and coplanar arc therapy optimization methods. Treatment planning is performed in three steps. First, a number of promising noncoplanar beam directions are selected using an iterative beam selection heuristic; these beams serve as anchor points of the arc therapy trajectory. In the second step, continuous gantry/couch angle trajectories are optimized using a simple combinatorial optimization model to define a beam trajectory that efficiently visits each of the anchor points. Treatment time is controlled by limiting the time the beam needs to trace the prescribed trajectory. In the third and final step, an optimal arc therapy plan is found along the prescribed beam trajectory. In principle any existing arc therapy optimization method could be incorporated into this step; for this work we use a sliding window VMAT algorithm. The approach is demonstrated using two particularly challenging cases. The first one is a lung SBRT patient whose planning goals could not be satisfied with fewer than nine noncoplanar IMRT fields when the patient was treated in the clinic. The second one is a brain tumor patient, where the target volume overlaps with the optic nerves and the chiasm and it is directly adjacent to the brainstem. Both cases illustrate that the large number of angles utilized by isocentric noncoplanar VMAT plans

  11. Feasibility of a unified approach to intensity-modulated radiation therapy and volume-modulated arc therapy optimization and delivery

    SciTech Connect

    Hoover, Douglas A. Chen, Jeff Z.; MacFarlane, Michael; Wong, Eugene; Battista, Jerry J.

    2015-02-15

    Purpose: To study the feasibility of unified intensity-modulated arc therapy (UIMAT) which combines intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) optimization and delivery to produce superior radiation treatment plans, both in terms of dose distribution and efficiency of beam delivery when compared with either VMAT or IMRT alone. Methods: An inverse planning algorithm for UIMAT was prototyped within the PINNACLE treatment planning system (Philips Healthcare). The IMRT and VMAT deliveries are unified within the same arc, with IMRT being delivered at specific gantry angles within the arc. Optimized gantry angles for the IMRT and VMAT phases are assigned automatically by the inverse optimization algorithm. Optimization of the IMRT and VMAT phases is done simultaneously using a direct aperture optimization algorithm. Five treatment plans each for prostate, head and neck, and lung were generated using a unified optimization technique and compared with clinical IMRT or VMAT plans. Delivery verification was performed with an ArcCheck phantom (Sun Nuclear) on a Varian TrueBeam linear accelerator (Varian Medical Systems). Results: In this prototype implementation, the UIMAT plans offered the same target dose coverage while reducing mean doses to organs at risk by 8.4% for head-and-neck cases, 5.7% for lung cases, and 3.5% for prostate cases, compared with the VMAT or IMRT plans. In addition, UIMAT can be delivered with similar efficiency as VMAT. Conclusions: In this proof-of-concept work, a novel radiation therapy optimization and delivery technique that interlaces VMAT or IMRT delivery within the same arc has been demonstrated. Initial results show that unified VMAT/IMRT has the potential to be superior to either standard IMRT or VMAT.

  12. Compact Dielectric Wall Accelerator Development For Intensity Modulated Proton Therapy And Homeland Security Applications

    SciTech Connect

    Chen, Y -; Caporaso, G J; Guethlein, G; Sampayan, S; Akana, G; Anaya, R; Blackfield, D; Cook, E; Falabella, S; Gower, E; Harris, J; Hawkins, S; Hickman, B; Holmes, C; Horner, A; Nelson, S; Paul, A; Pearson, D; Poole, B; Richardson, R; Sanders, D; Stanley, J; Sullivan, J; Wang, L; Watson, J; Weir, J

    2009-06-17

    Compact dielectric wall (DWA) accelerator technology is being developed at the Lawrence Livermore National Laboratory. The DWA accelerator uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube. Its high electric field gradients are achieved by the use of alternating insulators and conductors and short pulse times. The DWA concept can be applied to accelerate charge particle beams with any charge to mass ratio and energy. Based on the DWA system, a novel compact proton therapy accelerator is being developed. This proton therapy system will produce individual pulses that can be varied in intensity, energy and spot width. The system will be capable of being sited in a conventional linac vault and provide intensity modulated rotational therapy. The status of the developmental new technologies that make the compact system possible will be reviewed. These include, high gradient vacuum insulators, solid dielectric materials, SiC photoconductive switches and compact proton sources. Applications of the DWA accelerator to problems in homeland security will also be discussed.

  13. Short-term intensive family therapy for adolescent eating disorders: 30-month outcome.

    PubMed

    Marzola, Enrica; Knatz, Stephanie; Murray, Stuart B; Rockwell, Roxanne; Boutelle, Kerri; Eisler, Ivan; Kaye, Walter H

    2015-05-01

    Family therapy approaches have generated impressive empirical evidence in the treatment of adolescent eating disorders (EDs). However, the paucity of specialist treatment providers limits treatment uptake; therefore, our group developed the intensive family therapy (IFT)-a 5-day treatment based on the principles of family-based therapy for EDs. We retrospectively examined the long-term efficacy of IFT in both single-family (S-IFT) and multi-family (M-IFT) settings evaluating 74 eating disordered adolescents who underwent IFT at the University of California, San Diego, between 2006 and 2013. Full remission was defined as normal weight (≥ 95% of expected for sex, age, and height), Eating Disorder Examination Questionnaire (EDE-Q) global score within 1 SD of norms, and absence of binge-purging behaviours. Partial remission was defined as weight ≥ 85% of expected or ≥ 95% but with elevated EDE-Q global score and presence of binge-purging symptoms (<1/week). Over a mean follow-up period of 30 months, 87.8% of participants achieved either full (60.8%) or partial remission (27%), while 12.2% reported a poor outcome, with both S-IFT and M-IFT showing comparable outcomes. Short-term, intensive treatments may be cost-effective and clinically useful where access to regular specialist treatment is limited.

  14. Intensive combined modality therapy including low-dose TBI in high-risk Ewing's sarcoma patients

    SciTech Connect

    Kinsella, T.J.; Glaubiger, D.; Diesseroth, A.; Makuch, R.; Waller, B.; Pizzo, P.; Glatstein, E.

    1983-12-01

    Twenty-four high-risk Ewing's sarcoma patients were treated on an intensive combined modality protocol including low-dose fractionated total body irradiaiton (TBI) and autologous bone marrow infusion (ABMI). Twenty patients (83%) achieved a complete clinical response to the primary and/or metastatic sites following induction therapy. The median disease-free interval was 18 months, and nine patients remain disease-free with a follow-up of 22 to 72 months. Local failure as a manifestation of initial relapse occurred in only three patients (15%), each having synchronous distant failure. Eight patients failed initially with only distant metastases, usually within 1-2 years following a complete clinical response. Two patterns of granulocyte recovery following consolidative therapy (including TBI and ABMI) were recognized. The time to platelet recovery was different for the groups with early and late granulocyte recovery. Patients with late recovery did not tolerate maintenance chemotherapy. However, there was no difference in disease-free and overall survival, when comparing the groups with early and late granulocyte recovery. It is concluded that these high-risk Ewing's sarcoma patients remain a poor-prognosis group in spite of intensive combined modality therapy including low-dose TBI. The control of microscopic systemic disease remains the major challenge to improving the cure rate. A new combined modality protocol with high-dose 'therapeutic' TBI (800 rad/2 fractions) is being used and the protocol design is outlined.

  15. [Staphylococcal infections as an important problem in intensive therapy--own clinical observations].

    PubMed

    Czaban, Sławomir Lech; Olszańska, Dorota; Siemiatkowski, Andrzej

    2006-01-01

    The microbiological monitoring in the Intensive Care Units, in the last few years, revealed a significant increase of infections caused by Gram+ bacteria. Authors of multi-center studies focus upon the problems related to the treatment of the infections caused by the methicilline-resistant staphylococci (MRS) as well as to its spreading. The Staphylococcal infections were 26.6 % of all bacterial infections in the Intensive Care Unit of the Department of Anesthesiology and Intensive Care of the Medical Academy in Białystok, during one year observation. MRS rods counted 21.4% among all pathogens isolated from the specimens collected from the patients, undergoing the treatment in the ICU, and were responsible for 83.6% of all Staphylococcal infections. The analysis revealed the significant percentage MRS rods resistant to commonly used empirical antibiotic therapy. Our experience shows that vancomycin or linezolid should be used, as an empirical antibiotic therapy, in suspected MRS-caused severe infections along with the simultaneous monitoring of changes in G+ bacteria drug resistance and strict infection-control regime.

  16. Increasing Availability of Exposure Therapy Through Intensive Group Treatment for Childhood Anxiety and OCD.

    PubMed

    Whiteside, Stephen P H; Dammann, Julie E; Tiede, Michael S; Biggs, Bridget K; Hillson Jensen, Andrea

    2017-09-01

    Archival data were used to examine the feasibility of a 5-day, clinic-based, intensive exposure-based cognitive-behavioral group therapy for childhood anxiety disorders (CADs) and obsessive-compulsive disorder (OCD). Participants were 143 children (82 girls) aged 6 to 19 years ( M = 13.93 years, SD = 2.9 years) with CADs or OCD (or both) in 28 consecutive groups. Repeated-measures ANOVA in the subsample ( n = 57) with complete treatment data indicated positive change on all variables from pretreatment to posttreatment with few differences between CADs and OCD patients. Effect sizes were moderate to large for anxiety symptoms (parent reported = 0.74, child reported = 0.65) and impairment (parent reported = 1.02, child reported = 0.69). The intensive group protocol required fewer sessions and 36% fewer therapist-hours per patient than the individually administered protocol. The program increased treatment availability for families from diverse geographic areas ( M distance traveled to clinic = 407 miles, SD = 786.4 miles). These findings support further, well-controlled examination of the 5-day intensive group treatment protocol's efficacy and potential to increase availability of evidence-based exposure therapy.

  17. Brief intensive CBT for pediatric OCD with E-therapy maintenance.

    PubMed

    Farrell, Lara J; Oar, Ella L; Waters, Allison M; McConnell, Harry; Tiralongo, Evelin; Garbharran, Vinay; Ollendick, Thomas

    2016-08-01

    Cognitive behaviour therapy (CBT), incorporating exposure and response prevention (ERP), has received strong empirical support for the treatment of paediatric OCD, and moreover, is considered the first line treatment of choice (Geller & March, 2012). However, despite the availability of effective treatments for this chronic and debilitating disorder, only a small proportion of youth receive these evidence-based approaches. The present study aimed to examine the effectiveness of an intensive ERP-based treatment for youth OCD, using a multiple baseline controlled design. Children and youth (N=10; aged 11-16 years) with a primary diagnosis of OCD were randomly assigned to a 1- or 2-week baseline monitoring condition followed by the intervention. The efficacy of the intensive treatment, involving 1 session psychoeducation, 2-sessions ERP plus e-therapy maintenance was examined across parent- child- and clinician-rated measures at post-treatment and 6-month follow-up. Overall, there were significant reductions across time on almost all measures (except self-report anxiety), and moreover, the majority of the sample (80%) were considered reliably improved, and meeting clinically significant change. At post-treatment, 60% were in remission of symptoms, and at 6-month follow-up this increased to 70%. These findings provide strong support for intensive, time-limited approaches to ERP-based CBT for children and youth with OCD. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. SU-E-T-503: Intensity Modulated Proton Therapy (IMPT) Versus Intensity Modulated X-Ray Therapy (IMRT) for Patient with Hepatocellular Carcinoma: A Dosimetric Comparison

    SciTech Connect

    Singh, H; Zhao, L; Prabhu, K; Rana, S; Zheng, Y

    2015-06-15

    Purpose This study compares the dosimetric parameters in treatment of unresectable hepatocellular carcinoma between intensity modulated proton therapy (IMPT) and intensity modulated x-ray radiation therapy (IMRT). Methods and Materials: We studied four patients treated at our institution. All patients were simulated supine with 4D-CT using a GE light speed simulator with a maximum slice thickness of 3mm. The average CT and an internal target volume to account for respiration motion were used for planning. Both IMRT and IMPT plans were created using Elekta’s CMSXiO treatment planning system (TPS). The prescription dose was 58.05 CGE in 15 fractions. The IMRT plans had five beams with combination of co-planar and non-co-planar. The IMPT plans had 2 to 3 beams. Dose comparison was performed based on the averaged results of the four patients. Results The mean dose and V95% to PTV were 58.24CGE, 98.57% for IMPT, versus 57.34CGE and 96.68% for IMRT, respectively. The V10, V20, V30 and mean dose of the normal liver for IMPT were 23.10%, 18.61%, 13.75% and 9.78 CGE; and 47.19%, 37.55%, 22.73% and 17.12CGE for IMRT. The spinal cord didn’t receive any dose in IMPT technique, but received a maximum of 18.77CGE for IMRT. The IMPT gave lower maximum dose to the stomach as compared to IMRT (19.26 vs 26.35CGE). V14 for left and right kidney was 0% and 2.32% for IMPT and 3.89% and 29.54% for IMRT. The mean dose, V35, V40 and V45 for small bowl were similar in both techniques, 0.74CGE, 6.27cc, 4.85cc and 3.53 cc for IMPT, 3.47CGE, 9.73cc, 7.61cc 5.35cc for IMRT. Conclusion Based on this study, IMPT plans gave less dose to the critical structures such as normal liver, kidney, stomach and spinal cord as compared to IMRT plans, potentially leading to less toxicity and providing better quality of life for patients.

  19. Is high-intensity statin therapy associated with lower statin adherence compared with low- to moderate-intensity statin therapy? Implications of the 2013 American College of Cardiology/American Heart Association Cholesterol Management Guidelines.

    PubMed

    Virani, Salim S; Woodard, LeChauncy D; Akeroyd, Julia M; Ramsey, David J; Ballantyne, Christie M; Petersen, Laura A

    2014-11-01

    The recent cholesterol guideline recommends high-intensity statins in cardiovascular disease (CVD) patients. High-intensity statins are associated with more frequent side effects. Therefore, it may be of concern that these recommendations might reduce statin adherence. High-intensity statins are associated with lower adherence compared with low- to moderate-intensity statins. In a national database of 972,532 CVD patients from the Veterans Health Administration, we identified patients receiving statins between October 1, 2010, and September 30, 2011. We assessed statin adherence by calculating proportion of days covered (PDC) and determined whether high-intensity statin therapy was independently associated with a lower PDC. Statins were prescribed in 629,005 (64.7%). Of those, 229,437 (36.5%) received high-intensity statins. Mean PDC (0.87 vs 0.86, P < 0.0001) and patients with PDC ≥ 0.80 (76.3% vs 74.2%, P < 0.0001) were slightly higher for those receiving low- to moderate-intensity compared with high-intensity statins. In adjusted analyses, high-intensity statin use was associated with a significant but modest PDC reduction compared with low- to moderate-intensity statin use, whether PDC was assessed as a continuous (β-coefficient: -0.008, P < 0.0001) or categorical (PDC ≥ 0.80 [odds ratio: 0.94, 95% confidence interval: 0.93-0.96]) measure of statin adherence. An approach of high-intensity statin therapy will lead to a significant practice change, as the majority of CVD patients are not on high-intensity therapy. However, this change may be associated with a very modest reduction in statin adherence compared with low- to moderate-intensity therapy that is unlikely to be of clinical significance. © 2014 Wiley Periodicals, Inc.

  20. Progression of kidney disease in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin versus usual care: a report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

    PubMed

    Rahman, Mahboob; Baimbridge, Charles; Davis, Barry R; Barzilay, Joshua; Basile, Jan N; Henriquez, Mario A; Huml, Anne; Kopyt, Nelson; Louis, Gail T; Pressel, Sara L; Rosendorff, Clive; Sastrasinh, Sithiporn; Stanford, Carol

    2008-09-01

    Dyslipidemia is common in patients with chronic kidney disease. The role of statin therapy in the progression of kidney disease is unclear. Prospective randomized clinical trial, post hoc analyses. 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (lipid-lowering component) stratified by baseline estimated glomerular filtration rate (eGFR): less than 60, 60 to 89, and 90 or greater mL/min/1.73 m(2). Mean follow-up was 4.8 years. Randomized; pravastatin, 40 mg/d, or usual care. Total, high-density lipoprotein, and low-density lipoprotein cholesterol; end-stage renal disease (ESRD), eGFR. Through year 6, total cholesterol levels decreased in the pravastatin (-20.7%) and usual-care groups (-11.2%). No significant differences were seen between groups for rates of ESRD (1.36 v 1.45/100 patient-years; P = 0.9), composite end points of ESRD and 50% or 25% decrease in eGFR, or rate of change in eGFR. Findings were consistent across eGFR strata. In patients with eGFR of 90 mL/min/1.73 m(2) or greater, the pravastatin arm tended to have a higher eGFR. Proteinuria data unavailable, post hoc analyses, unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range, statin drop-in rate in usual-care group with small cholesterol differential between groups. In hypertensive patients with moderate dyslipidemia and decreased eGFR, pravastatin was not superior to usual care in preventing clinical renal outcomes. This was consistent across the strata of baseline eGFR. However, benefit from statin therapy may depend on the degree of the cholesterol level decrease achieved.

  1. Progression of Kidney Disease in Moderately Hypercholesterolemic, Hypertensive Patients Randomized to Pravastatin Versus Usual Care: A Report From the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

    PubMed Central

    Rahman, Mahboob; Baimbridge, Charles; Davis, Barry R.; Barzilay, Joshua; Basile, Jan N.; Henriquez, Mario A.; Huml, Anne; Kopyt, Nelson; Louis, Gail T.; Pressel, Sara L.; Rosendorff, Clive; Sastrasinh, Sithiporn; Stanford, Carol

    2009-01-01

    Background Dyslipidemia is common in patients with chronic kidney disease. The role of statin therapy on the progression of kidney disease is unclear. Study Design Prospective randomized clinical trial, post hoc analyses. Setting and participants 10,060 participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (lipid-lowering component) stratified by baseline eGFR: <60, 60–89, ≥90 mL/min/1.73 m2. Mean follow-up was 4.8 years. Intervention Randomized, pravastatin 40 mg/day or usual care. Outcomes and measurements Total cholesterol, HDL- and LDL-cholesterol; end stage renal disease (ESRD), estimated glomerular filtration rate (eGFR). Results Through year six, total cholesterol declined in the pravastatin (−20.7%) and usual care groups (−11.2%). No significant differences were seen between the groups for rates of ESRD (1.36 vs 1.45/100 patient years, P=0.9), composite endpoints of ESRD and 50% or 25% decline in eGFR, or rate of change of eGFR. Findings were consistent across eGFR strata. In patients with eGFR≥90 mL/min/1.73 m2, the pravastatin arm tended to have a higher eGFR. Limitations Proteinuria data unavailable, post hoc analyses, unconfirmed validity of the Modification of Diet in Renal Disease Study equation in normal eGFR range, statin drop-in rate in usual care group with small cholesterol differential between groups. Conclusions In hypertensive patients with moderate dyslipidemia and reduced eGFR, pravastatin was not superior to usual care in preventing clinical renal outcomes. This was consistent across the strata of baseline eGFR. However, benefit from statin therapy may depend on degree of cholesterol reduction achieved. PMID:18676075

  2. Optimization of intensity-modulated very high energy (50-250 MeV) electron therapy

    NASA Astrophysics Data System (ADS)

    Yeboah, C.; Sandison, G. A.; Moskvin, V.

    2002-04-01

    This work evaluates the potential of very high energy (50-250 MeV) electron beams for dose conformation and identifies those variables that influence optimized dose distributions for this modality. Intensity-modulated plans for a prostate cancer model were optimized as a function of the importance factors, beam energy and number of energy bins, number of beams, and the beam orientations. A trial-and-error-derived constellation of importance factors for target and sensitive structures to achieve good conformal dose distributions was 500, 50, 10 and 1 for the target, rectum, bladder and normal tissues respectively. Electron energies greater than 100 MeV were found to be desirable for intensity-modulated very high energy electron therapy (VHEET) of prostate cancer. Plans generated for lower energy beams had relatively poor conformal dose distributions about the target region and delivered high doses to sensitive structures. Fixed angle beam treatments utilizing a large number of fields in the range 9-21 provided acceptable plans. Using more than 21 beams at fixed gantry angles had an insignificant effect on target coverage, but resulted in an increased dose to sensitive structures and an increased normal tissue integral dose. Minor improvements in VHEET plans utilizing a `small' number (=<9) of beams may be achieved if, in addition to intensity modulation, energy modulation is implemented using a small number (=<3) of beam energies separated by 50 to 100 MeV. Rotation therapy provided better target dose homogeneity but unfortunately resulted in increased rectal dose, bladder dose and normal tissue integral dose relative to the 21-field fixed angle treatment plan. Modulation of the beam energy for rotation therapy had no beneficial consequences on the optimized dose distributions. Lastly, selection of beam orientations influenced the optimized treatment plan even when a large number of beams (approximately 15) were employed.

  3. Intensity-Modulated Radiation Therapy with Stereotactic Body Radiation Therapy Boost for Unfavorable Prostate Cancer: The Georgetown University Experience.

    PubMed

    Mercado, Catherine; Kress, Marie-Adele; Cyr, Robyn A; Chen, Leonard N; Yung, Thomas M; Bullock, Elizabeth G; Lei, Siyuan; Collins, Brian T; Satinsky, Andrew N; Harter, K William; Suy, Simeng; Dritschilo, Anatoly; Lynch, John H; Collins, Sean P

    2016-01-01

    Stereotactic body radiation therapy (SBRT) is emerging as a minimally invasive alternative to brachytherapy to deliver highly conformal, dose--escalated radiation therapy (RT) to the prostate. SBRT alone may not adequately cover the tumor extensions outside the prostate commonly seen in unfavorable prostate cancer. External beam radiation therapy (EBRT) with high dose rate brachytherapy boost is a proven effective therapy for unfavorable prostate cancer. This study reports on early prostate-specific antigen and prostate cancer-specific quality of life (QOL) outcomes in a cohort of unfavorable patients treated with intensity-modulated radiation therapy (IMRT) and SBRT boost. Prostate cancer patients treated with SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) from March 2008 to September 2012 were included in this retrospective review of prospectively collected data. Biochemical failure was assessed using the Phoenix definition. Patients completed the expanded prostate cancer index composite (EPIC)-26 at baseline, 1 month after the completion of RT, every 3 months for the first year, then every 6 months for a minimum of 2 years. One hundred eight patients (4 low-, 45 intermediate-, and 59 high-risk) with median age of 74 years completed treatment, with median follow-up of 4.4 years. Sixty-four percent of the patients received androgen deprivation therapy prior to the initiation of RT. The 3-year actuarial biochemical control rates were 100 and 89.8% for intermediate- and high-risk patients, respectively. At the initiation of RT, 9 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. Mean EPIC urinary and bowel function and bother scores exhibited transient declines, with subsequent return to near baseline. At 2 years posttreatment, 13.7 and 5% of men felt their urinary and bowel function was a moderate to big problem, respectively. At 3-year follow-up, biochemical control

  4. Extracorporeal liver support therapy with Prometheus in patients with liver failure in the intensive care unit.

    PubMed

    Oppert, Michael; Rademacher, Sibylle; Petrasch, Kathrin; Jörres, Achim

    2009-10-01

    Acute liver failure (ALF) and acute-on-chronic liver failure (AoCLF) are associated with a high mortality. In these patients an accumulation of both water-soluble and water-insoluble, protein-bound, metabolic waste products occurs. Conventional extracorporeal blood purification techniques based on diffusion and/or convection such as hemodialysis or hemofiltration may only eliminate small molecular weight, water-soluble compounds. In recent years, fractionated plasma separation and adsorption (FPSA) with the Prometheus system has been introduced for extracorporeal liver support therapy. To date, however, only limited data is available regarding the effect of this treatment on mortality and outcome of patients with advanced liver disease. Here we report on our experience with 23 patients with severe liver failure who were treated with Prometheus in our medical intensive care unit. Fourteen patients had AoCLF, and nine patients experienced ALF. The median bilirubin level at the start of Prometheus therapy was 30.5 mg/dL and the median Acute Physiology and Chronic Health Evaluation II (APACHE II) score was 26. During 40 individual treatment sessions lasting 5-6 h, Prometheus therapy reduced serum bilirubin levels from 23.7 mg/dL to 15.0 mg/dL (median values) (P < 0.001), and the overall survival was 26%. ALF patients had a better survival compared to AoCLF patients (44% vs. 22%; P = 0.022). Apart from one patient who developed hemodynamic instability during a treatment session, Prometheus therapy was well tolerated without relevant side-effects. In conclusion, extracorporeal liver support therapy with Prometheus is a novel and safe treatment option in patients with severe liver failure. In this series, patients with ALF showed a significantly better outcome with Prometheus therapy compared to AoCLF patients.

  5. Multidisciplinary team of intensive therapy: humanization and fragmentation of the work process.

    PubMed

    Evangelista, Viviane Canhizares; Domingos, Thiago da Silva; Siqueira, Fernanda Paula Cerântola; Braga, Eliana Mara

    2016-01-01

    to understand the meaning of humanized care in intensive care units considering the experience of the multidisciplinary team. descriptive and exploratory qualitative research. For this purpose, we conducted semi-structured interviews with 24 professionals of the heath-care team, and, after transcription, we organized the qualitative data according to content analysis. from two main categories, we were able to understand that humanized care is characterized in the actions of health-care: effective communication, team work, empathy, singularity, and integrality; and mischaracterized in the management processes, specifically in the fragmentation of the work process and health-care, in the precarious work conditions, and in differing conceptual aspects of the political proposal of humanization. care activities in intensive therapy are guided by the humanization of care and corroborate the hospital management as a challenge to be overcome to boost advances in the operationalization of this Brazilian policy.

  6. High-intensity laser therapy during chronic degenerative tenosynovitis experimentally induced in broiler chickens

    NASA Astrophysics Data System (ADS)

    Fortuna, Damiano; Rossi, Giacomo; Bilotta, Teresa W.; Zati, Allesandro; Gazzotti, Valeria; Venturini, Antonio; Pinna, Stefania; Serra, Christian; Masotti, Leonardo

    2002-10-01

    The aims of this study was the safety and the efficacy of High Intensity Laser Therapy (HILT) on chronic degenerative tenosynovitis. We have effectuated the histological evaluation and seroassay (C reactive protein) on 18 chickens affect by chronic degenerative tenosynovitis experimentally induced. We have been employed a Nd:YAG laser pulsed wave; all irradiated subjects received the same total energy (270 Joule) with a fluence of 7,7 J/cm2 and intensity of 10,7 W/cm2. The histological findings revealed a distinct reduction of the mineralization of the choral matrix, the anti-inflammatory effect of the laser, the hyperplasia of the synoviocytes and ectasia of the lymphatic vessels.

  7. Perturbative diffusion theory formalism for interpreting temporal light intensity changes during laser interstitial thermal therapy.

    PubMed

    Chin, Lee C L; Whelan, William M; Vitkin, I Alex

    2007-03-21

    In an effort to understand dynamic optical changes during laser interstitial thermal therapy (LITT), we utilize the perturbative solution of the diffusion equation in heterogeneous media to formulate scattering weight functions for cylindrical line sources. The analysis explicitly shows how changes in detected interstitial light intensity are associated with the extent and location of the volume of thermal coagulation during treatment. Explanations for previously reported increases in optical intensity observed early during laser heating are clarified using the model and demonstrated with experimental measurements in ex vivo bovine liver tissue. This work provides an improved understanding of interstitial optical signal changes during LITT and indicates the sensitivity and potential of interstitial optical monitoring of thermal damage.

  8. [Reversible cerebral vasoconstriction syndrome. Challenge for diagnostics and intensive care therapy].

    PubMed

    Jansen, G; Mertzlufft, F; Bach, F

    2015-08-01

    Reversible cerebral vasoconstriction syndrome (RCVS) is a disease of unclear incidence frequently affecting middle aged women and is usually associated with use of adrenergic or serotoninergic substances. The exclusion of relevant differential diagnoses, such as aneurysmal subarachnoid hemorrhage, primary cerebral angiitis, posterior reversible encephalopathy syndrome and carotid artery dissection is critical in terms of time and significance. Thunderclap headache as well as multiple and multilocular vasospasms with direct or indirect angiography without substantial findings in cerebrospinal fluid diagnostics are typical symptoms. The necessity for intensive care treatment is often justified by initial acute impairment of vital functions and possible development of cerebral or extracerebral complications. Because the exact pathophysiology remains unknown, a specific therapy does not exist. This poses significant challenges in intensive care medicine, which are illustrated on the basis of the case study presented.

  9. A beam intensity monitor for the Loma Linda cancer therapy proton accelerator.

    PubMed

    Coutrakon, G; Miller, D; Kross, B J; Anderson, D F; DeLuca, P; Siebers, J

    1991-01-01

    A beam intensity monitor was tested in a 230-MeV proton beam at the Loma Linda Proton Therapy Accelerator during its commissioning at Fermi National Accelerator Laboratory. The intensity monitor was designed to regulate the beam intensity extracted from the proton synchrotron. The proton beam is tunable between 70 and 250 MeV with an adjustable intensity between 10(10) and 10(11) protons per spill. A beam spill is typically 1 s long with a 2-s repetition period. The intensity monitor must be radiation hard, expose minimum mass to the beam, and measure intensity to 1% in 1-ms time intervals. To this end, a 5-cm-thick xenon gas scintillator optically coupled to a photomultiplier tube (PMT) was tested to measure its response to the proton beam. The gas cell was operated at 1.2 atm of pressure and has 12.7-microns-thick titanium entrance and exit foils. The total mass exposed to the beam is 0.14 g/cm2 and is dominated by the titanium windows. This mass corresponds to a range attenuation equal to 1.4 mm of water. The energy lost to the xenon gas is about 70 keV per proton. Each passing proton will produce approximately 2000 photons. With a detection efficiency on the order of 0.05% for this UV light, one would anticipate over 10(10) photoelectrons per second. In a 1-ms time bin there will be approximately 10(7) photoelectrons. This yields a resolution limited by systematics. For unregulated 0.4-s proton spills, we observe a response bandwidth in excess of 10(4) Hz. While signal-to-noise and linearity were not easily measured, we estimate as few as 10(3) protons can be observed suggesting a dynamic range in excess of 10(5) is available.

  10. Therapy/imaging array-based system and technology for intense ultrasound surgery

    NASA Astrophysics Data System (ADS)

    Barthe, Peter G.; Slayton, Michael H.; Jaeger, Paul M.; Makin, Inder R. S.; Gallagher, Laura A.; Mast, T. Douglas; Runk, Megan M.; Faidi, Waseem

    2004-05-01

    Minimally invasive, miniature (2.2- × 50-mm aperture, 3.3-mm diameter) dual-mode linear arrays have been developed into low-cost disposable probes with high acoustic power output (120 W/cm2 at the source), high transmit efficiency (>65% typical), and good imaging performance (50% fractional bandwidth, >100-mm-deep field of view). These therapy/imaging probes have been integrated into a flexible intense ultrasound surgery platform which also includes conventional diagnostic imaging probes. A system architecture has been developed which includes a 64-channel therapy driver with software selection of array aperture and phasing (λ/16), frequency (0.5-8 MHz), drive amplitude (5 W/channel, nominal), rotational steering (+/-180 deg), and temporal sequencing/switching of imaging/therapy/monitoring modes. System software includes graphical and text-based script mode control of therapeutic treatment. Real-time monitoring of electric power per channel, temperature sensors, and thermal effects provide a range of feedback and safety. Numerous system and probe technological issues such as electrical interconnect and matching, acoustic coupling, thermal control, and maintaining probe efficiency have been addressed. The array-based imaging/therapy system has produced encouraging results in preclinical studies of bulk tissue ablation and imaging.

  11. A compact linac for intensity modulated proton therapy based on a dielectric wall accelerator.

    PubMed

    Caporaso, G J; Mackie, T R; Sampayan, S; Chen, Y-J; Blackfield, D; Harris, J; Hawkins, S; Holmes, C; Nelson, S; Paul, A; Poole, B; Rhodes, M; Sanders, D; Sullivan, J; Wang, L; Watson, J; Reckwerdt, P J; Schmidt, R; Pearson, D; Flynn, R W; Matthews, D; Purdy, J

    2008-06-01

    A novel compact CT-guided intensity modulated proton radiotherapy (IMPT) system is described. The system is being designed to deliver fast IMPT so that larger target volumes and motion management can be accomplished. The system will be ideal for large and complex target volumes in young patients. The basis of the design is the dielectric wall accelerator (DWA) system being developed at the Lawrence Livermore National Laboratory (LLNL). The DWA uses fast switched high voltage transmission lines to generate pulsed electric fields on the inside of a high gradient insulating (HGI) acceleration tube. High electric field gradients are achieved by the use of alternating insulators and conductors and short pulse times. The system will produce individual pulses that can be varied in intensity, energy and spot width. The IMPT planning system will optimize delivery characteristics. The system will be capable of being sited in a conventional linac vault and provide intensity modulated rotational therapy. Feasibility tests of an optimization system for selecting the position, energy, intensity and spot size for a collection of spots comprising the treatment are underway. A prototype is being designed and concept designs of the envelope and environmental needs of the unit are beginning. The status of the developmental new technologies that make the compact system possible will be reviewed. These include, high gradient vacuum insulators, solid dielectric materials, SiC photoconductive switches and compact proton sources.

  12. TH-A-BRE-01: The Status of Intensity Modulated Proton and Ion Therapy

    SciTech Connect

    Dong, L; Zhu, X; Unkelbach, J; Schulte, R

    2014-06-15

    IMRT with photons has become a radiation therapy standard of care for many cancer treatment sites. The situation is quite different with intensity modulated particle (protons and ion) radiation therapy (IMPT). With the rapid development of beam scanning techniques and many of the newer proton facilities exclusively offering active beam scanning as their radiation delivery technique, it is timely to give an update on the status and challenges of IMPT. The leading principle in IMPT is to aim at the target from several, not necessarily coplanar, directions with multiple pencil beams that are modulated in their intensity and adjusted in their energy such that a desired dose distribution or, more generally, a desired bio-effective dose distribution is achieved. Different from low-LET photons, the varying relative biological effectiveness (RBE) along the beam path adds an additional dimension to the treatment planning process and will require biophysical modeling at least for carbon ion therapy. IMPT involves computationally challenging tasks, yet it needs to be very fast in order to be clinically relevant. To make IMPT computationally tractable, robust and efficient optimization methods are required. Lastly, IMPT planning is very sensitive to accurate knowledge of relative stopping and scattering powers of the intervening tissues as well as intra- and inter-fraction motion. Robust planning methods are being developed in order to obtain IMPT plans that are less sensitive against such uncertainties. This therapy symposium will present an update on the current status and emerging developments of IMPT from the medical physics perspective. Learning Objectives: Become familiar with current delivery techniques for IMPT and their limitations. Understand the basics of dose calculational algorithms and commissioning of IMPT. Learn how to assess the accuracy of planning and delivery of IMPT treatments. Get an overview of currently used and emerging optimization techniques. Learn

  13. Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

    PubMed

    Wright, Jackson T; Harris-Haywood, Sonja; Pressel, Sara; Barzilay, Joshua; Baimbridge, Charles; Bareis, Charles J; Basile, Jan N; Black, Henry R; Dart, Richard; Gupta, Alok K; Hamilton, Bruce P; Einhorn, Paula T; Haywood, L Julian; Jafri, Syed Z A; Louis, Gail T; Whelton, Paul K; Scott, Cranford L; Simmons, Debra L; Stanford, Carol; Davis, Barry R

    2008-01-28

    Antihypertensive drugs with favorable metabolic effects are advocated for first-line therapy in hypertensive patients with metabolic/cardiometabolic syndrome (MetS). We compared outcomes by race in hypertensive individuals with and without MetS treated with a thiazide-type diuretic (chlorthalidone), a calcium channel blocker (amlodipine besylate), an alpha-blocker (doxazosin mesylate), or an angiotensin-converting enzyme inhibitor (lisinopril). A subgroup analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind hypertension treatment trial of 42 418 participants. We defined MetS as hypertension plus at least 2 of the following: fasting serum glucose level of at least 100 mg/dL, body mass index (calculated as weight in kilograms divided by height in meters squared) of at least 30, fasting triglyceride levels of at least 150 mg/dL, and high-density lipoprotein cholesterol levels of less than 40 mg/dL in men or less than 50 mg/dL in women. Significantly higher rates of heart failure were consistent across all treatment comparisons in those with MetS. Relative risks (RRs) were 1.50 (95% confidence interval, 1.18-1.90), 1.49 (1.17-1.90), and 1.88 (1.42-2.47) in black participants and 1.25 (1.06-1.47), 1.20 (1.01-1.41), and 1.82 (1.51-2.19) in nonblack participants for amlodipine, lisinopril, and doxazosin comparisons with chlorthalidone, respectively. Higher rates for combined cardiovascular disease were observed with lisinopril-chlorthalidone (RRs, 1.24 [1.09-1.40] and 1.10 [1.02-1.19], respectively) and doxazosin-chlorthalidone comparisons (RRs, 1.37 [1.19-1.58] and 1.18 [1.08-1.30], respectively) in black and nonblack participants with MetS. Higher rates of stroke were seen in black participants only (RR, 1.37 [1.07-1.76] for the lisinopril-chlorthalidone comparison, and RR, 1.49 [1.09-2.03] for the doxazosin-chlorthalidone comparison). Black patients with MetS also had higher rates of end

  14. History of Pu'er Tea and comparative study for the effect of its various extracts on lipid-lowering diet.

    PubMed

    Qiong, Sun; Xishuang, Yan

    2014-07-01

    Pu'er Tea is a kind of traditional historical famous tea which gains its name for native government jurisdiction in Pu'er (now Xishuangbanna in Yunnan, Pu'er city etc), and takes Pu'er (now Ninger county of Pu'er city) city as its collecting and distributing center .It is famous all over the world because of its good benefits for reducing blood lipid, slimming weight, antibacterial, aid digestion, detoxification and other functions, it is even known as the health care beverage with "the fine quality goods for preserving people's health", "a health drink demanded everyday". Although there are a lot of current study literature about the effect of Pu'er Tea on lipid-lowering and reducing weight, but there is rarely contrast study about the effect of lipid-lowering diet with its various extracts. Therefore, this article uses the acetone, water, chloroform, ethyl acetate and n-butanol to continuously extract Pu'er Tea, then freeze and dry them into four major separate components which include the chloroform layer, ethyl acetate layer, butanol layer and the remaining water layer. Take advantage of different components for filling and feeding the ICR mice which are treated with the processing of obesity molding, then compare the extract of Pu'er Tea with the weight-loss drug L-carnitine which is popular all over the market, explore the slimming effect of each component in Pu'er Tea on the cells of ICR fat mice. The results show that the total water extract of Pu'er Tea, ethyl acetate extract, residual water extract all have obvious effect on reducing body weight and body fat of experimental mice, it also has significant lowering effect on blood lipid and liver lipid in mice, that could significantly inhibit the accumulation of lipid in fat cells and hypertrophy of fat cells, reveal that the Pu'er Tea has good function of lipid-lowering and reducing weight. At the same time, the comprehensive effect of lipid-lowering and reducing weight through Pu 'er Tea is superior to

  15. Dose-Volume Comparison of Proton Therapy and Intensity-Modulated Radiotherapy for Prostate Cancer

    SciTech Connect

    Vargas, Carlos Fryer, Amber; Mahajan, Chaitali; Indelicato, Daniel; Horne, David C.; Chellini, Angela; McKenzie, Craig C.; Lawlor, Paula C.; Henderson, Randal; Li Zuofeng; Lin Liyong; Olivier, Kenneth; Keole, Sameer

    2008-03-01

    Purpose: The contrast in dose distribution between proton radiotherapy (RT) and intensity-modulated RT (IMRT) is unclear, particularly in regard to critical structures such as the rectum and bladder. Methods and Materials: Between August and November 2006, the first 10 consecutive patients treated in our Phase II low-risk prostate proton protocol (University of Florida Proton Therapy Institute protocol 0001) were reviewed. The double-scatter proton beam plans used in treatment were analyzed for various dosimetric endpoints. For all plans, each beam dose distribution, angle, smearing, and aperture margin were optimized. IMRT plans were created for all patients and simultaneously analyzed. The IMRT plans were optimized through multiple volume objectives, beam weighting, and individual leaf movement. The patients were treated to 78 Gray-equivalents (GE) in 2-GE fractions with a biologically equivalent dose of 1.1. Results: All rectal and rectal wall volumes treated to 10-80 GE (percentage of volume receiving 10-80 GE [V{sub 10}-V{sub 80}]) were significantly lower with proton therapy (p < 0.05). The rectal V{sub 50} was reduced from 31.3% {+-} 4.1% with IMRT to 14.6% {+-} 3.0% with proton therapy for a relative improvement of 53.4% and an absolute benefit of 16.7% (p < 0.001). The mean rectal dose decreased 59% with proton therapy (p < 0.001). For the bladder and bladder wall, proton therapy produced significantly smaller volumes treated to doses of 10-35 GE (p < 0.05) with a nonsignificant advantage demonstrated for the volume receiving {<=}60 GE. The bladder V{sub 30} was reduced with proton therapy for a relative improvement of 35.3% and an absolute benefit of 15.1% (p = 0.02). The mean bladder dose decreased 35% with proton therapy (p = 0.002). Conclusion: Compared with IMRT, proton therapy reduced the dose to the dose-limiting normal structures while maintaining excellent planning target volume coverage.

  16. Interactions between CYP3A5*3 and POR*28 polymorphisms and lipid lowering response with atorvastatin.

    PubMed

    Wei, Kan-kan; Zhang, Li-rong

    2015-09-01

    The polymorphic enzyme P450 oxidoreductase (POR) transfers electrons from nicotinamide adenine dinucleotide phosphate (NADPH) to cytochrome P450 (CYP) 3A enzyme s, which metabolize atorvastatin. This suggests that variations in the CYP3A5 and POR genes may influence the response to statins. We aimed to investigate the association and interactions between CYP3A5*3 and POR*28 polymorphisms and the lipid-lowering effects of atorvastatin in a Chinese population. Genotypes were determined by polymerase chain reaction (PCR) with restriction fragment length polymorphism analysis and by PCR with direct sequencing analysis for 179 hyperlipidaemic patients treated with atorvastatin 20 mg once daily for 4 weeks. Serum levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were determined before and after treatment. For the 179 patients (including 100 males), the variant allele frequencies of CYP3A5*3 and POR*28 were 73.75 and 41.62 %, respectively. Among all patients, no significant association was found between CYP3A5*3 polymorphisms and TG, TC, LDL-C and HDL-C levels before and after treatment with 20 mg of atorvastatin daily for 4 weeks. Homozygotes for the POR*28 T allele showed a significantly lower mean concentration of LDL-C than homozygotes for the POR*28 C allele (POR*28 TT vs POR*28 CC: 2.46 ± 0.37 vs 2.69 ± 0.49 mmol/L, P = 0.019) after treatment with atorvastatin 20 mg daily for 4 weeks. After adjustment for age, sex and body mass index, CYP3A5 non-expressors who were POR*28 wild-type homozygotes showed significantly higher mean TC and LDL-C levels than those who were POR*28 variant homozygotes, both at baseline (*3/CC vs *3/TT; TC: 7.30 ± 0.73 vs 6.94 ± 0.36 mmol/L, P = 0.026; LDL-C: 3.88 ± 0.70 vs 3.47 ± 0.46 mmol/L, P = 0.009) and after atorvastatin treatment (*3/CC vs *3/TT; TC: 6.03 ± 0.64 vs 5.69 ± 0.34 mmol/L, P = 0

  17. Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

    SciTech Connect

    Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

    2013-12-15

    Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose–volume histogram (DVH) doses were consistently lower. The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques.

  18. Carcinoma of the anal canal: Intensity modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3DCRT)

    PubMed Central

    Sale, Charlotte; Moloney, Phillip; Mathlum, Maitham

    2013-01-01

    Introduction Patients with anal canal carcinoma treated with standard conformal radiotherapy frequently experience severe acute and late toxicity reactions to the treatment area. Roohipour et al. (Dis Colon Rectum 2008; 51: 147–53) stated a patient's tolerance of chemoradiation to be an important prediction of treatment success. A new intensity modulated radiation therapy (IMRT) technique for anal carcinoma cases has been developed at the Andrew Love Cancer Centre aimed at reducing radiation to surrounding healthy tissue. Methods A same-subject repeated measures design was used for this study, where five anal carcinoma cases at the Andrew Love Cancer Centre were selected. Conformal and IMRT plans were generated and dosimetric evaluations were performed. Each plan was prescribed a total of 54 Gray (Gy) over a course of 30 fractions to the primary site. Results The IMRT plans resulted in improved dosimetry to the planning target volume (PTV) and reduction in radiation to the critical structures (bladder, external genitalia and femoral heads). Statistically there was no difference between the IMRT and conformal plans in the dose to the small and large bowel; however, the bowel IMRT dose–volume histogram (DVH) doses were consistently lower. Conclusion The IMRT plans were superior to the conformal plans with improved dose conformity and reduced radiation to the surrounding healthy tissue. Anecdotally it was found that patients tolerated the IMRT treatment better than the three-dimensional (3D) conformal radiation therapy. This study describes and compares the planning techniques. PMID:26229623

  19. Family-Based Cognitive-Behavioral Therapy for Pediatric Obsessive-Compulsive Disorder: Comparison of Intensive and Weekly Approaches

    ERIC Educational Resources Information Center

    Storch, Eric A.; Geffken, Gary R.; Merlo, Lisa J.; Mann, Giselle; Duke, Danny; Munson, Melissa; Adkins, Jennifer; Grabill, Kristen M.; Murphy, Tanya K.; Goodman, Wayne K.

    2007-01-01

    Objective: To examine the relative efficacy of intensive versus weekly cognitive-behavioral therapy (CBT) for children and adolescents with obsessive-compulsive disorder (OCD). Method: Forty children and adolescents with OCD (range 7-17 years) were randomized to receive 14 sessions of weekly or intensive (daily psychotherapy sessions) family-based…

  20. Family-Based Cognitive-Behavioral Therapy for Pediatric Obsessive-Compulsive Disorder: Comparison of Intensive and Weekly Approaches

    ERIC Educational Resources Information Center

    Storch, Eric A.; Geffken, Gary R.; Merlo, Lisa J.; Mann, Giselle; Duke, Danny; Munson, Melissa; Adkins, Jennifer; Grabill, Kristen M.; Murphy, Tanya K.; Goodman, Wayne K.

    2007-01-01

    Objective: To examine the relative efficacy of intensive versus weekly cognitive-behavioral therapy (CBT) for children and adolescents with obsessive-compulsive disorder (OCD). Method: Forty children and adolescents with OCD (range 7-17 years) were randomized to receive 14 sessions of weekly or intensive (daily psychotherapy sessions) family-based…

  1. Acupuncture and Traditional Herbal Medicine Therapy Prevent Deliriumin Patients with Cardiovascular Disease in Intensive Care Units.

    PubMed

    Matsumoto-Miyazaki, Jun; Ushikoshi, Hiroaki; Miyata, Shusaku; Miyazaki, Nagisa; Nawa, Takahide; Okada, Hideshi; Ojio, Shinsuke; Ogura, Shinji; Minatoguchi, Shinya

    2017-02-23

    The aim of this study was to determine the effect of combination therapy consisting of acupuncture and traditional herbal medicine (Kampo medicine) for reducing the incidence rate of delirium in patients with cardiovascular (CV) disease in ICUs. Twenty-nine patients who had been urgently admitted to the ICU in the control period were treated with conventional intensive care. Thirty patients in the treatment period received conventional therapy plus a combination therapy consisting of acupuncture and herbal medicine. Acupuncture treatment was performed once a day, and the herbal formula was administered orally three times a day during the first week of the ICU stay. The standard acupuncture points were GV20, Ex-HN3, HT7, LI4, Liv3, and KI3, and the main herbal preparation was Kamikihito. The incident rates of delirium, assessed using the confusion assessment method for ICU, in the treatment and control period were compared. The incidence rate of delirium was significantly lower in the treatment group than in the control group (6.6% vs. 37.9%, [Formula: see text]). Moreover, sedative drugs and non-pharmacological approaches against aggressive behavior of patients who were delirious were used less in the treatment group than in the control group. No serious adverse events were observed in the treatment group. Combination therapy consisting of acupuncture and herbal medicine was found to be effective in lowering the incidence of delirium in patients with CV disease in ICUs. Further studies with a large sample size and parallel randomized controlled design would be required to establish the effects of this therapy.

  2. Imaging Changes in Pediatric Intracranial Ependymoma Patients Treated With Proton Beam Radiation Therapy Compared to Intensity Modulated Radiation Therapy

    SciTech Connect

    Gunther, Jillian R.; Sato, Mariko; Chintagumpala, Murali; Ketonen, Leena; Jones, Jeremy Y.; Allen, Pamela K.; Paulino, Arnold C.; Okcu, M. Fatih; Su, Jack M.; Weinberg, Jeffrey; Boehling, Nicholas S.; Khatua, Soumen; Adesina, Adekunle; Dauser, Robert; Whitehead, William E.; Mahajan, Anita

    2015-09-01

    Purpose: The clinical significance of magnetic resonance imaging (MRI) changes after radiation therapy (RT) in children with ependymoma is not well defined. We compared imaging changes following proton beam radiation therapy (PBRT) to those after photon-based intensity modulated RT (IMRT). Methods and Materials: Seventy-two patients with nonmetastatic intracranial ependymoma who received postoperative RT (37 PBRT, 35 IMRT) were analyzed retrospectively. MRI images were reviewed by 2 neuroradiologists. Results: Sixteen PBRT patients (43%) developed postradiation MRI changes at 3.8 months (median) with resolution by 6.1 months. Six IMRT patients (17%) developed changes at 5.3 months (median) with 8.3 months to resolution. Mean age at radiation was 4.4 and 6.9 years for PBRT and IMRT, respectively (P=.06). Age at diagnosis (>3 years) and time of radiation (≥3 years) was associated with fewer imaging changes on univariate analysis (odds ratio [OR]: 0.35, P=.048; OR: 0.36, P=.05). PBRT (compared to IMRT) was associated with more frequent imaging changes, both on univariate (OR: 3.68, P=.019) and multivariate (OR: 3.89, P=.024) analyses. Seven (3 IMRT, 4 PBRT) of 22 patients with changes had symptoms requiring intervention. Most patients were treated with steroids; some PBRT patients also received bevacizumab and hyperbaric oxygen therapy. None of the IMRT patients had lasting deficits, but 2 patients died from recurrent disease. Three PBRT patients had persistent neurological deficits, and 1 child died secondarily to complications from radiation necrosis. Conclusions: Postradiation MRI changes are more common with PBRT and in patients less than 3 years of age at diagnosis and treatment. It is difficult to predict causes for development of imaging changes that progress to clinical significance. These changes are usually self-limiting, but some require medical intervention, especially those involving the brainstem.

  3. Intensive insulin therapy for preventing postoperative infection in patients with traumatic brain injury

    PubMed Central

    Wang, Yan; Li, Jin-ping; Song, Ying-lun; Zhao, Qi-huang

    2017-01-01

    Abstract Objective: To assess the effect of intensive insulin therapy (IIT) for preventing postoperative infection in patients with traumatic brain injury (TBI). Methods: In total, 88 patients with TBI were randomly divided into 2 groups, 44 in each group. One group (group ITT) received IIT and the other group (group CIT) received conventional insulin therapy (CIT). This study was conducted between February 2013 and January 2016. Outcomes included infection rate, mortality, and neurological outcome (measured by the Glasgow Outcome Scale [GOS]). Results: A total of 81 patients completed the study. IIT showed greater efficacy than CIT, with a decreased infection rate in the IIT group compared to the CIT group (31.9% vs 52.3%, P = 0.03), and also a reduced duration of stay in intensive care unit (ICU) (IIT group, 4.5 ± 2.1 days vs CIT group, 5.7 ± 2.8 days, P = 0.02). In addition, a significant difference in scores on the GOS scale was observed between the 2 groups (P = 0.04). The mortality rates in hospital and at the 26-week follow-up were similar between the 2 groups. Conclusion: IIT leads to a reduced infection rate, shorter stays in ICU, and improved neurological outcome. PMID:28353579

  4. Intensity modulated radiation therapy with field rotation--a time-varying fractionation study.

    PubMed

    Dink, Delal; Langer, Mark P; Rardin, Ronald L; Pekny, Joseph F; Reklaitis, Gintaras V; Saka, Behlul

    2012-06-01

    This paper proposes a novel mathematical approach to the beam selection problem in intensity modulated radiation therapy (IMRT) planning. The approach allows more beams to be used over the course of therapy while limiting the number of beams required in any one session. In the proposed field rotation method, several sets of beams are interchanged throughout the treatment to allow a wider selection of beam angles than would be possible with fixed beam orientations. The choice of beamlet intensities and the number of identical fractions for each set are determined by a mixed integer linear program that controls jointly for the distribution per fraction and the cumulative dose distribution delivered to targets and critical structures. Trials showed the method allowed substantial increases in the dose objective and/or sparing of normal tissues while maintaining cumulative and fraction size limits. Trials for a head and neck site showed gains of 25%-35% in the objective (average tumor dose) and for a thoracic site gains were 7%-13%, depending on how strict the fraction size limits were set. The objective did not rise for a prostate site significantly, but the tolerance limits on normal tissues could be strengthened with the use of multiple beam sets.

  5. Occupational Therapy for Patients With Acute Lung Injury: Factors Associated With Time to First Intervention in the Intensive Care Unit

    PubMed Central

    Dinglas, Victor D.; Colantuoni, Elizabeth; Ciesla, Nancy; Mendez-Tellez, Pedro A.; Shanholtz, Carl

    2013-01-01

    OBJECTIVE. Very early occupational therapy intervention in the intensive care unit (ICU) improves patients’ physical recovery. We evaluated the association of patient, ICU, and hospital factors with time to first occupational therapy intervention in ICU patients with acute lung injury (ALI). METHOD. We conducted a prospective cohort study of 514 consecutive patients with ALI from 11 ICUs in three hospitals in Baltimore, MD. RESULTS. Only 30% of patients ever received occupational therapy during their ICU stay. Worse organ failure, continuous hemodialysis, and uninterrupted continuous infusion of sedation were independently associated with delayed occupational therapy initiation, and hospital study site and admission to a trauma ICU were independently associated with earlier occupational therapy. CONCLUSION. Severity of illness and ICU practices for sedation administration were associated with delayed occupational therapy. Both hospital study site and type of ICU were independently associated with timing of occupational therapy, indicating modifiable environmental factors for promoting early occupational therapy in the ICU. PMID:23597694

  6. A tale of two trials: a comparison of the post-acute coronary syndrome lipid-lowering trials A to Z and PROVE IT-TIMI 22.

    PubMed

    Wiviott, Stephen D; de Lemos, James A; Cannon, Christopher P; Blazing, Michael; Murphy, Sabina A; McCabe, Carolyn H; Califf, Robert; Braunwald, Eugene

    2006-03-21

    The Aggrastat to Zocor (A to Z) and Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trials compared intensive and moderate statin therapy after acute coronary syndromes, with seemingly disparate results. We analyzed the design, implementation, and results of the two trials in an attempt to clarify the effects of early intensive statin therapy. Study design, end points, and definitions were compared. In each trial, comparisons were made between intensive and moderate arms for both trials' primary end points and death/myocardial infarction. Analyses were performed over various time points: at the end of the trials, < or =4 months, and >4 months. Subjects in A to Z had higher-risk demographics. More PROVE IT subjects were enrolled in the United States and underwent prerandomization revascularization. The low-density lipoprotein (LDL) difference was greater in A to Z than in PROVE IT early (< or =4 months) but less late. Significant C-reactive protein reduction was earlier in PROVE IT. With common end points, event rates were higher in A to Z, and early favorable separation of event curves was seen in PROVE IT but not in A to Z. Clinical end point rates and reductions were similar in both trials after 4 months. An early benefit was seen in PROVE IT but not in A to Z. Late-phase results were similar. Factors that may explain this disparity include the intensity of therapy in the early phase, timing, and magnitude of LDL and C-reactive protein lowering, differences in early revascularization, and the play of chance. Taken together, the results of these trials support a strategy of early intensive statin therapy coupled with revascularization when appropriate in patients after acute coronary syndrome.

  7. Intensive Statin Therapy in NSTE-ACS Patients Undergoing PCI: Clinical and Biochemical Effects

    PubMed Central

    Fayez, George; Nassar, Ahmed

    2015-01-01

    Early initiation of statin therapy in acute coronary syndrome patients has a favorable prognostic impact because of its anti-inflammatory and antithrombotic properties. In this study, we explored the effect of atorvastatin-loading, followed by intensive atorvastatin therapy, on clinical and biochemical outcomes in non-ST-segment-elevation acute coronary syndrome patients who were scheduled for percutaneous coronary intervention. We prospectively enrolled 140 patients (mean age, 56 ± 9 years, 68% men). Once eligible, patients were randomly assigned to receive either a moderate 20-mg daily dose of atorvastatin (Group A) or a 160-mg loading dose followed by an intensified 80-mg daily dose (Group B). High-sensitivity C-reactive protein (hs-CRP) levels were recorded before and after intervention. Evaluation after 6 months included hs-CRP levels, left ventricular systolic function, and major adverse cardiac events. We found no significant difference between the 2 groups in regard to the interventional data. However, blood sampling after coronary intervention, and again 6 months later, revealed a significant decline in mean hs-CRP level among Group B patients (P <0.001). Moreover, patients in Group B manifested a higher left ventricular ejection fraction than did patients in Group A (P <0.05). After 6 months, we found no significant difference between groups in the incidence of major adverse cardiac events. We conclude that intensive atorvastatin therapy in non-ST-segment-elevation acute coronary syndrome patients is associated with lower hs-CRP levels and with higher left ventricular ejection fraction after 6 months, with no significant impact on adverse cardiac events. PMID:26664304

  8. Impact of admission to hospice on pain intensity and type of pain therapies administered.

    PubMed

    Petracci, Elisabetta; Nanni, Letizia; Maltoni, Marco; Derni, Stefania; Campana, Gabriele; Scarpi, Emanuela

    2016-01-01

    The primary aim of this study was to evaluate pain intensity changes in patients admitted to a hospice. The secondary objective was to evaluate whether these changes in pain were accompanied by modifications in therapies and drugs used to treat pain. This retrospective study included 96 patients admitted to a hospice for a minimum of 7 days who received pain therapy. An 11-point (0-10) numerical rating scale (NRS) was used to assess pain on a daily basis. A repeated measures analysis of variance was performed to evaluate pain intensity changes over time. Mean ± SD pain NRS values of the entire group were 2.58 ± 2.61 on day 1 and 1.40 ± 1.72 on day 7 (P = 0.002). Restricting the analysis to patients with moderate to severe pain at the time of hospice admission, results were even more significant. In fact, mean ± SD pain NRS was 5.51 ± 1.24 for patients with pain ≥4 at admission and 1.76 ± 1.91 for the same patients after 7 days (P < 0.001). A significant increase in the number of patients receiving morphine was observed from day 1 to day 7 (24 to 41, respectively, P = 0.001) and in those receiving drugs via parenteral routes (subcutaneous or intravenous) from 10 to 27 (P = 0.002) CONCLUSIONS: Admission to a hospice and the hospice environment led to a significant reduction in reported pain intensity for the patients included in this study, mainly those with moderate to severe pain at the time of admission. This decrease in pain was accompanied by a significant increase in the use of morphine, especially via parenteral routes, but not by a higher mean equivalent daily dose of oral morphine per patient.

  9. [Overview and perspectives of mesenchymal stem cell therapy in intensive care medicine].

    PubMed

    Espinoza, Francisco; Aliaga, Felipe; Crawford, Patricia Luz

    2016-02-01

    Development of innovative therapies in intensive care medicine is particularly important since diseases as sepsis, acute respiratory distress syndrome (ARDS) and acute renal injury (AKI) have an elevated morbidity and mortality in spite of current gold-standard approaches. Mesenchymal stem cells (MSC) may have a promising role due to their properties in immunomodulation, tissue reparation and microbial clearance. Preclinical data and results of a systematic review of PubMed, PMC and ClinicalTrials.gov have been included to review the role of MSC therapy in sepsis, ARDS and AKI. A description of MSC biology, sources and benefits in preclinical models was included. A phase I/II clinical trial (RCT) is recruiting neutropenic patients with septic shock. In ARDS, the START trial (Stem cells in ARDS Treatment) is a phase I/II study of bone marrow-derived human MSC (hMSC) that is currently recruiting patients. In AKI, a phase I study has demonstrated the safety of hMSCs infusion in patients undergoing cardiac surgery with high risk to develop AKI. A phase II study is still active. The results of these studies will determine the real feasibility of MSC therapy in critically ill patients.

  10. Backscatter monitoring of high intensity focused ultrasound therapy using a parametric treatment model

    NASA Astrophysics Data System (ADS)

    Speyer, Gavriel; Kaczkowski, Peter; Brayman, Andrew; Crum, Lawrence

    2010-03-01

    Accurate monitoring of high intensity focused ultrasound (HIFU) surgery is critical to ensuring proper treatment. Pulse-echo diagnostic ultrasound (DU) is a recognized modality for identifying temperature differentials using speckle tracking between two DU radio frequency (RF) frames [2], [4]. This observation has motivated non-parametric temperature estimation, which associates temperature changes directly with the displacement estimates. We present an estimation paradigm termed displacement mode analysis (DMA), which uses physical modeling to associate particular patterns of observed displacement, called displacement modes, with corresponding modes of variation in the administered therapy. This correspondence allows DMA to estimate therapy directly using a linear combination of displacement modes, imbuing these displacement estimates into the reference using interpolation, and by aligning with the treatment frame, providing a therapy estimate with the heating modes. Since DMA is maximum likelihood estimation (MLE), the accuracy of its estimates can be assessed a priori, providing error bounds for estimates of applied heating, temperature, and thermal dose. Predicted performance is verified using both simulation and experiment for a point exposure of 4.2 Watts of electrical power in alginate, a tissue mimicking phantom.

  11. Intensity-modulated radiation therapy to bilateral lower limb extremities concurrently: a planning case study

    SciTech Connect

    Fitzgerald, Emma Miles, Wesley; Fenton, Paul; Frantzis, Jim

    2014-09-15

    Non-melanomatous skin cancers represent 80% of all newly diagnosed cancers in Australia with basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) being the most common. A previously healthy 71-year-old woman presented with widespread and tender superficial skin cancers on the lower bilateral limbs. External beam radiation therapy through the use of intensity-modulated radiation therapy (IMRT) was employed as the treatment modality of choice as this technique provides conformal dose distribution to a three-dimensional treatment volume while reducing toxicity to surrounding tissues. The patient was prescribed a dose of 60 Gy to the planning target volume (PTV) with 1.0 cm bolus over the ventral surface of each limb. The beam arrangement consisted of six treatment fields that avoided entry and exit through the contralateral limb. The treatment plans met the International Commission on Radiation Units and Measurements (ICRU) guidelines and produced highly conformal dosimetric results. Skin toxicity was measured against the National Cancer Institute: Common Terminology Criteria for Adverse Events (NCI: CTCAE) version 3. A well-tolerated treatment was delivered with excellent results given the initial extent of the disease. This case study has demonstrated the feasibility and effectiveness of IMRT for skin cancers as an alternative to surgery and traditional superficial radiation therapy, utilising a complex PTV of the extremities for patients with similar presentations.

  12. [Bacterial contamination as a complication of intravenous therapy in intensive care (author's transl)].

    PubMed

    Kilian, J; Hösch, A; Ahnefeld, F W; Schmitz, J E; Vanek, E

    1980-10-01

    Intravenous infusion therapy has become an indispensible part of intensive care. Problems of bacterial contamination during this therapy are well known. To check on the possible routes of contamination we examined the infusion system in its several parts (infusion solution, infusion system, connection between infusion system and catheter and content of syringes). The highest rate of contamination was found at the connection between the infusion system and the catheter after use for 24 h (26.7%, 39 out of 146 probes); just at the beginning of the infusion we found bacterial growth in 7.1% (10 out of 141 probes). After injection of drugs into the system the infusion solution was contaminated in 1.9% (6 of 320 probes). The system for measuring the central venous pressure was contaminated in 2.7% (4 of 148 probes). At the end of infusion the infusion solutions were contaminated in 3.1% (9 of 287 probes). Different drugs in syringes in no case were contaminated. In most cases (59 probes) we found gram-positive bacteria (87.3%), in only seven cases (9.7%) gram-negative bacterias and in two cases Candida tropicalis. Our results show that the extrinsic or in use contamination plays the most important part in bacterial contamination of the infusion system. Infection control of intravenous therapy necessitates care in the hygienic standard adopted during the infusion and injection procedures.

  13. Improved outcomes with intensity modulated radiation therapy combined with temozolomide for newly diagnosed glioblastoma multiforme.

    PubMed

    Aherne, Noel J; Benjamin, Linus C; Horsley, Patrick J; Silva, Thomaz; Wilcox, Shea; Amalaseelan, Julan; Dwyer, Patrick; Tahir, Abdul M R; Hill, Jacques; Last, Andrew; Hansen, Carmen; McLachlan, Craig S; Lee, Yvonne L; McKay, Michael J; Shakespeare, Thomas P

    2014-01-01

    Purpose. Glioblastoma multiforme (GBM) is optimally treated by maximal debulking followed by combined chemoradiation. Intensity modulated radiation therapy (IMRT) is gaining widespread acceptance in other tumour sites, although evidence to support its use over three-dimensional conformal radiation therapy (3DCRT) in the treatment of gliomas is currently lacking. We examined the survival outcomes for patients with GBM treated with IMRT and Temozolomide. Methods and Materials. In all, 31 patients with GBM were treated with IMRT and 23 of these received chemoradiation with Temozolomide. We correlated survival outcomes with patient functional status, extent of surgery, radiation dose, and use of chemotherapy. Results. Median survival for all patients was 11.3 months, with a median survival of 7.2 months for patients receiving 40.05 Gray (Gy) and a median survival of 17.4 months for patients receiving 60 Gy. Conclusions. We report one of the few series of IMRT in patients with GBM. In our group, median survival for those receiving 60 Gy with Temozolomide compared favourably to the combined therapy arm of the largest randomised trial of chemoradiation versus radiation to date (17.4 months versus 14.6 months). We propose that IMRT should be considered as an alternative to 3DCRT for patients with GBM.

  14. Leaf-sequencing for intensity-modulated arc therapy using graph algorithms

    SciTech Connect

    Luan Shuang; Wang Chao; Cao Daliang; Chen, Danny Z.; Shepard, David M.; Yu, Cedric X.

    2008-01-15

    Intensity-modulated arc therapy (IMAT) is a rotational IMRT technique. It uses a set of overlapping or nonoverlapping arcs to create a prescribed dose distribution. Despite its numerous advantages, IMAT has not gained widespread clinical applications. This is mainly due to the lack of an effective IMAT leaf-sequencing algorithm that can convert the optimized intensity patterns for all beam directions into IMAT treatment arcs. To address this problem, we have developed an IMAT leaf-sequencing algorithm and software using graph algorithms in computer science. The input to our leaf-sequencing software includes (1) a set of (continuous) intensity patterns optimized by a treatment planning system at a sequence of equally spaced beam angles (typically 10 deg. apart), (2) a maximum leaf motion constraint, and (3) the number of desired arcs, k. The output is a set of treatment arcs that best approximates the set of optimized intensity patterns at all beam angles with guaranteed smooth delivery without violating the maximum leaf motion constraint. The new algorithm consists of the following key steps. First, the optimized intensity patterns are segmented into intensity profiles that are aligned with individual MLC leaf pairs. Then each intensity profile is segmented into k MLC leaf openings using a k-link shortest path algorithm. The leaf openings for all beam angles are subsequently connected together to form 1D IMAT arcs under the maximum leaf motion constraint using a shortest path algorithm. Finally, the 1D IMAT arcs are combined to form IMAT treatment arcs of MLC apertures. The performance of the implemented leaf-sequencing software has been tested for four treatment sites (prostate, breast, head and neck, and lung). In all cases, our leaf-sequencing algorithm produces efficient and highly conformal IMAT plans that rival their counterpart, the tomotherapy plans, and significantly improve the IMRT plans. Algorithm execution times ranging from a few seconds to 2 min are

  15. Different effects of antihypertensive regimens based on fosinopril or hydrochlorothiazide with or without lipid lowering by pravastatin on progression of asymptomatic carotid atherosclerosis: principal results of PHYLLIS--a randomized double-blind trial.

    PubMed

    Zanchetti, Alberto; Crepaldi, Gaetano; Bond, M Gene; Gallus, Giuseppe; Veglia, Fabrizio; Mancia, Giuseppe; Ventura, Alessandro; Baggio, Giovannella; Sampieri, Lorena; Rubba, Paolo; Sperti, Giovanni; Magni, Alberto

    2004-12-01

    The Plaque Hypertension Lipid-Lowering Italian Study (PHYLLIS) tested whether (1) the angiotensin-converting enzyme (ACE) inhibitor fosinopril (20 mg per day) was more effective on carotid atherosclerosis progression than the diuretic hydrochlorothiazide (25 mg per day), (2) pravastatin (40 mg per day) was more effective than placebo when added to either hydrochlorothiazide or fosinopril, and (3) there were additive effects of ACE inhibitor and lipid-lowering therapies. A total of 508 hypertensive, hypercholesterolemic patients with asymptomatic carotid atherosclerosis were randomized to: (A) hydrochlorothiazide; (B) fosinopril; (C) hydrochlorothiazide plus pravastatin; and (D) fosinopril plus pravastatin, and followed up blindly for 2.6 years. B-Mode carotid scans were performed yearly by certified sonographers in 13 hospitals and read centrally. Corrections for drift were calculated from readings repeated at study end. Primary outcome was change in mean maximum intima-media thickness of far and near walls of common carotids and bifurcations bilaterally (CBM(max)). CBM(max) significantly progressed (0.010+/-0.004 mm per year; P=0.01) in group A (hydrochlorothiazide alone) but not in groups B, C, and D. CBM(max) changes in groups B, C, and D were significantly different from changes in group A. Changes in group A were concentrated at the bifurcations. "Clinic" and "ambulatory" blood pressure reductions were not significantly different between groups, but total and low-density lipoprotein cholesterol decreased by approximately 1 mmol/L in groups C and D. Progression of carotid atherosclerosis occurred with hydrochlorothiazide but not with fosinopril. Progression could also be avoided by associating pravastatin with hydrochlorothiazide.

  16. Comparison of diet quality, physical activity and biochemical values of older adults either reporting or not reporting use of lipid-lowering medication.

    PubMed

    Lofgren, I; Greene, G; Schembre, S; Delmonico, M J; Riebe, D; Clark, P

    2010-02-01

    The aim of this study was to compare standard lipid profile, reported dietary intake, and physical activity in older adults who reported taking or not taking a lipid-lowering medication, namely statins. Cross-sectional study utilizing baseline data collected from a subsample of a larger randomized clinical trial, The Study of Exercise and Nutrition in Older Rhode Islanders (SENIOR) Project. A total of 115 participants, 33 males and 82 females, over the age of 60, community-dwelling, primarily retired, and from East Providence, Rhode Island and surrounding communities in Rhode Island and Massachusetts. Height and weight were measured and used to calculate body mass index. Waist circumference was measured. Medical history and medication use surveys were completed. Dietary assessment was done via three 24 hour recalls using NDS-R. The Yale Physical Activity Survey was used to determine energy expenditure during exercise and a physical activity summary score. Fasting blood samples were obtained to determine lipid profile. 37 participants (32.2%) reported taking lipid-lowering medication, statins exclusively, and 78 (67.8%) reported not taking any lipid-lowering medication. Participants who reported taking statins had better lipid profiles than those participants who reported not taking statins but had significantly lower intakes of vitamin B12, vitamin K, calcium, and potassium. There were no differences between groups on reported physical activity. However, the mean intakes for both groups did not meet the Dietary Reference Intakes for multiple nutrients. Older adults need additional education on the importance of lifestyle changes in reducing CHD risk, whether taking lipid-lowering medications or not.

  17. Application of Jean Piaget's theory of human development for nursing children in an adult intensive therapy unit.

    PubMed

    Green, A

    1991-12-01

    Piaget (1964) believed that interaction with the environment has a large part to play in human development. Matthew (1986) states that in an ideal world critically ill children should be cared for by staff trained in paediatrics, within designated paediatric intensive therapy units. Unfortunately, there are only 28 paediatric intensive therapy units in Great Britain (CMA Medical Data, 1987), consequently each year a third of children requiring intensive care are admitted to adult intensive therapy units (ITU). A knowledge and understanding of developmental psychology can therefore be beneficial to nurses in assessing which stage of development a child has reached, in order to plan the correct level of stimulation, and hence facilitate progress rather than regression in the accomplishment of developmental tasks. The psychological and social processes involved in Jean Piaget's (1896-1980) theory of human development are discussed with regard to nursing children requiring intubation and ventilation in an adult ITU.

  18. Potential Lipid-Lowering Effects of Eleusine indica (L) Gaertn. Extract on High-Fat-Diet-Induced Hyperlipidemic Rats.

    PubMed

    Ong, Siew Ling; Nalamolu, Koteswara Rao; Lai, How Yee

    2017-01-01

    To date, anti-obesity agents based on natural products are tested for their potential using lipase inhibition assay through the interference of hydrolysis of fat by lipase resulting in reduced fat absorption without altering the central mechanisms. Previous screening study had indicated strong anti-obesity potential in Eleusine indica (E. indica), but to date, no pharmacologic studies have been reported so far. This study was performed to investigate the lipid-lowering effects of E. indica using both in vitro and in vivo models. The crude methanolic extract of E. indica was fractionated using hexane (H-Ei), dichloromethane (DCM-Ei), ethyl acetate (EA-Ei), butanol (B-Ei), and water (W-Ei). All the extracts were tested for antilipase activity using porcine pancreatic lipase. Because H-Ei showed the highest inhibition, it was further subjected to chemical profiling using high-performance liquid chromatography. Subsequently, oral toxicity analysis of H-Ei was performed [Organization for Economic Cooperation and Development guidelines using fixed dose procedure (No. 420)]; efficacy analysis was performed using high-fat diet (HFD)-induced hyperlipidemic female Sprague-Dawley rats. According to the toxicity and efficacy analyses, H-Ei did not demonstrate any noticeable biochemical toxicity or physiologic abnormalities and did not cause any tissue damage as per histologic analysis. Furthermore, H-Ei significantly reduced body weight and improved serum profile and did not show hepatotoxicity and nephrotoxicity based on the serum profile. Moreover, H-Ei alleviated HFD-induced hepatosteatosis and ameliorated induced adiposity in both visceral and subcutaneous adipose tissue. Our results demonstrate that H-Ei effectively improved hyperlipidemia. Further studies to explore its possibility as an alternative pharmacologic agent to treat obesity are warranted. Hexane extract of Eleusine indica (H-Ei) showed strong potential in the inhibition of porcine pancreatic lipase (27.01

  19. Efficacy and tolerability of a combined lipid-lowering nutraceutical on cholesterolemia, hs-CRP level and endothelial function in moderately hypercholesterolemic subjects.

    PubMed

    Cicero, A F; Colletti, A; Rosticci, M; Grandi, E; Borghi, C

    2016-01-01

    Our aim was to test, by a double-blind, placebo-controlled randomized clinical trial, whether a short-term treatment with a combined lipid-lowering nutraceutical could improve endothelial function in a cohort of moderately hypercholesterolemic subjects. Thus, 80 healthy, moderately hypercholesterolemic subjects were consecutively enrolled and, after 4 weeks of stabilization diet, they were randomized to either the tested lipid-lowering nutraceutical or placebo for 8 weeks. At the beginning and end of treatment a complete lipid pattern, safety parameters, hs-CRP and endothelial function were measured. When compared to placebo, during nutraceutical treatment patients experienced a more favorable percentage change in total cholesterol (TC vs baseline: -17.9%; TC vs placebo: -5.6%), LDL-cholesterol (LDL-C vs baseline: -23.3%; LDL-C vs placebo: -2.8%), hs-CRP (hs-CRP vs baseline: -2.4%; hs-CRP vs placebo: -1.5%), and endothelial function (pulse volume displacement vs baseline: +17%; pulse volume displacement vs placebo treatment: -3.3%). No significant difference was observed in respect to effects on triglycerides, HDL-cholesterol and safety parameters. On the basis of our data, the tested lipid-lowering nutraceutical seems to significantly improve endothelial function in moderately hypercholesterolemic subjects. These results have to be confirmed on larger patient samples and over longer periods.

  20. Clinical response of advanced cancer patients to cellular immunotherapy and intensity-modulated radiation therapy

    PubMed Central

    Hasumi, Kenichiro; Aoki, Yukimasa; Wantanabe, Ryuko; Mann, Dean L

    2013-01-01

    Patients afflicted with advanced cancers were treated with the intratumoral injection of autologous immature dendritic cells (iDCs) followed by activated T-cell infusion and intensity-modulated radiation therapy (IMRT). A second round of iDCs and activated T cells was then administered to patients after the last radiation cycle. This complete regimen was repeated for new and recurring lesions after 6 weeks of follow-up. One year post therapy, outcome analyses were performed to evaluate treatment efficacy. Patients were grouped according to both the number and size of tumors and clinical parameters at treatment initiation, including recurrent disease after standard cancer therapy, Stage IV disease, and no prior therapy. Irrespective of prior treatment status, 23/37 patients with ≤ 5 neoplastic lesions that were ≤ 3 cm in diameter achieved complete responses (CRs), and 5/37 exhibited partial responses (PRs). Among 130 individuals harboring larger and more numerous lesions, CRs were observed in 7/74 patients that had received prior SCT and in 2/56 previously untreated patients. Some patients manifested immune responses including an increase in CD8+CD56+ lymphocytes among circulating mononuclear cells in the course of treatment. To prospectively explore the therapeutic use of these cells, CD8+ cells were isolated from patients that had been treated with cellular immunotherapy and IMRT, expanded in vitro, and injected into recurrent metastatic sites in 13 individuals who underwent the same immunoradiotherapeutic regimens but failed to respond. CRs were achieved in 34 of 58 of such recurrent lesions while PRs in 17 of 58. These data support the expanded use of immunoradiotherapy in advanced cancer patients exhibiting progressive disease. PMID:24349874

  1. Analysis of Survival After Initiation of Continuous Renal Replacement Therapy in a Surgical Intensive Care Unit.

    PubMed

    Tatum, James M; Barmparas, Galinos; Ko, Ara; Dhillon, Navpreet; Smith, Eric; Margulies, Daniel R; Ley, Eric J

    2017-06-21

    Continuous renal replacement therapy (CRRT) benefits patients with renal failure who are too hemodynamically unstable for intermittent hemodialysis. The duration of therapy beyond which continued use is futile, particularly in a population of patients admitted to and primarily cared for by a surgical service (hereinafter referred to as surgical patients), is unclear. To analyze proportions of and independent risk factors for survival to discharge after initiation of CRRT among patients in a surgical intensive care unit (SICU). This retrospective cohort study included all patients undergoing CRRT from July 1, 2012, through January 31, 2016, in an SICU of an urban tertiary medical center. The population included patients treated before or after general surgery and patients admitted to a surgical service during inpatient evaluation and care before liver transplant. The pretransplant population was censored from further survival analysis on receipt of a transplant. Continuous renal replacement therapy. Hospital mortality among patients in an SICU after initiation of CRRT. Of 108 patients (64 men [59.3%] and 44 women [40.7%]; mean [SD] age, 62.0 [12.7] years) admitted to the SICU, 53 were in the general surgical group and 55 in the pretransplant group. Thirteen of the 22 patients in the pretransplant group who required 7 or more days of CRRT died (in-hospital mortality, 59.1%); among the 12 patients in the general surgery group who required 7 or more days of CRRT, 12 died (in-hospital mortality, 100%). In the general surgical group, each day of CRRT was associated with an increased adjusted odds ratio of death of 1.39 (95% CI, 1.01-1.90; P = .04). Continuous renal replacement therapy is valuable for surgical patients with an acute and correctable indication; however, survival decreases significantly with increasing duration of CRRT. Duration of CRRT does not correlate with survival among patients awaiting liver transplant.

  2. Bridging the gap between IMRT and VMAT: Dense angularly sampled and sparse intensity modulated radiation therapy

    SciTech Connect

    Li, Ruijiang; Xing, Lei

    2011-09-15

    Purpose: To propose an alternative radiation therapy (RT) planning and delivery scheme with optimal angular beam sampling and intrabeam modulation for improved dose distribution while maintaining high delivery efficiency. Methods: In the proposed approach, coined as dense angularly sampled and sparse intensity modulated RT (DASSIM-RT), a large number of beam angles are used to increase the angular sampling, leading to potentially more conformal dose distributions as compared to conventional IMRT. At the same time, intensity modulation of the incident beams is simplified to eliminate the dispensable segments, compensating the increase in delivery time caused by the increased number of beams and facilitating the plan delivery. In a sense, the proposed approach shifts and transforms, in an optimal fashion, some of the beam segments in conventional IMRT to the added beams. For newly available digital accelerators, the DASSIM-RT delivery can be made very efficient by concatenating the beams so that they can be delivered sequentially without operator's intervention. Different from VMAT, the level of intensity modulation in DASSIS-RT is field specific and optimized to meet the need of each beam direction. Three clinical cases (a head and neck (HN) case, a pancreas case, and a lung case) are used to evaluate the proposed RT scheme. DASSIM-RT, VMAT, and conventional IMRT plans are compared quantitatively in terms of the conformality index (CI) and delivery efficiency. Results: Plan quality improves generally with the number and intensity modulation of the incident beams. For a fixed number of beams or fixed level of intensity modulation, the improvement saturates after the intensity modulation or number of beams reaches to a certain level. An interplay between the two variables is observed and the saturation point depends on the values of both variables. For all the cases studied here, the CI of DASSIM-RT with 15 beams and 5 intensity levels (0.90, 0.79, and 0.84 for the HN

  3. Bridging the gap between IMRT and VMAT: Dense angularly sampled and sparse intensity modulated radiation therapy

    PubMed Central

    Li, Ruijiang; Xing, Lei

    2011-01-01

    Purpose: To propose an alternative radiation therapy (RT) planning and delivery scheme with optimal angular beam sampling and intrabeam modulation for improved dose distribution while maintaining high delivery efficiency. Methods: In the proposed approach, coined as dense angularly sampled and sparse intensity modulated RT (DASSIM-RT), a large number of beam angles are used to increase the angular sampling, leading to potentially more conformal dose distributions as compared to conventional IMRT. At the same time, intensity modulation of the incident beams is simplified to eliminate the dispensable segments, compensating the increase in delivery time caused by the increased number of beams and facilitating the plan delivery. In a sense, the proposed approach shifts and transforms, in an optimal fashion, some of the beam segments in conventional IMRT to the added beams. For newly available digital accelerators, the DASSIM-RT delivery can be made very efficient by concatenating the beams so that they can be delivered sequentially without operator’s intervention. Different from VMAT, the level of intensity modulation in DASSIS-RT is field specific and optimized to meet the need of each beam direction. Three clinical cases (a head and neck (HN) case, a pancreas case, and a lung case) are used to evaluate the proposed RT scheme. DASSIM-RT, VMAT, and conventional IMRT plans are compared quantitatively in terms of the conformality index (CI) and delivery efficiency. Results: Plan quality improves generally with the number and intensity modulation of the incident beams. For a fixed number of beams or fixed level of intensity modulation, the improvement saturates after the intensity modulation or number of beams reaches to a certain level. An interplay between the two variables is observed and the saturation point depends on the values of both variables. For all the cases studied here, the CI of DASSIM-RT with 15 beams and 5 intensity levels (0.90, 0.79, and 0.84 for the

  4. Hypofractionated Intensity-Modulated Arc Therapy for Lymph Node Metastasized Prostate Cancer

    SciTech Connect

    Fonteyne, Valerie; De Gersem, Werner; De Neve, Wilfried; Jacobs, Filip; Lumen, Nicolaas; Vandecasteele, Katrien; Villeirs, Geert; De Meerleer, Gert

    2009-11-15

    Purpose: To determine the planning results and acute toxicity after hypofractionated intensity-modulated arc radiotherapy and androgen deprivation for lymph node metastasized (Stage N1) prostate cancer. Methods and Materials: A total of 31 patients with Stage T1-T4N1M0 prostate cancer were treated with intensity-modulated arc radiotherapy and 3 years of androgen deprivation as primary treatment. The clinical target volume (CTV{sub p}) was the prostate and seminal vesicles. Elective lymph node areas ({sub e}) were delineated and expanded by 2 mm to create the CTV{sub e}. The planning target volumes (PTV{sub p} and PTV{sub e}) were created using a three-dimensional expansion of the CTV{sub p} and CTV{sub e}, respectively, of 7 mm. A median dose of 69.3 Gy and 50 Gy was prescribed to the PTV{sub p} and PTV{sub e} respectively, to be delivered in 25 fractions. Upper and lower gastrointestinal toxicity was scored using the Radiation Therapy Oncology Group toxicity and radiotherapy-induced lower intestinal toxicity scoring system. Genitourinary toxicity was scored using a combined Radiation Therapy Oncology Group, LENT-SOMA (late effects normal tissue-subjective, objective, management, analytic), and Common Toxicity Criteria toxicity scoring system. Results: The median follow-up time was 3 months. The mean prescription dose to the CTV{sub p} and PTV{sub p} was 70.4 Gy and 68.6 Gy, respectively. The minimal dose to the CTV{sub e} and PTV{sub e} was 49.0 Gy and 47.0 Gy, respectively. No acute Grade 2 or greater gastrointestinal toxicity occurred. Fourteen patients developed acute Grade 2 lower gastrointestinal toxicity. Acute Grade 3 and 2 genitourinary toxicity developed in 2 and 14 patients, respectively. Conclusion: The results of our study have shown that hypofractionated intensity-modulated arc radiotherapy as primary therapy for N1 prostate cancer is feasible with low toxicity.

  5. Clinical predictors of aminoglycoside-induced ototoxicity in drug-resistant Tuberculosis patients on intensive therapy.

    PubMed

    Sogebi, Olusola Ayodele; Adefuye, Bolanle Olufunlola; Adebola, Stephen Oluwatosin; Oladeji, Susan Modupe; Adedeji, Taiwo Olugbemiga

    2017-08-01

    The study objectives were to determine the incidence of aminoglycoside-induced ototoxicity in institutionalized patients on intensive phase of therapy for drug-resistant Tuberculosis (DR Tb) and also to assess clinical factors which could predict the ototoxicity. The study was a prospective analytical study among consecutive DR Tb patients who were admitted for intensive phase of therapy (of 4 months) at the DR-Tb center over a 12-month period. Patients were diagnosed as DR Tb using the Gene Xpert machine to confirm Rifampicin resistance. All eligible 70 out of 87 consenting patients were consecutively recruited into the study. Patients had baseline (admission) and serial pure tone audiometries (PTAs) performed at 4 weekly intervals until discharge after 4 months of admission. Audiometric confirmation of aminoglycoside-induced ototoxicity was done by comparing serial with baseline PTA. Among the 70 patients the male:female ratio was 1.7:1. Nine patients (12.9%) were retroviral-positive, and 16 patients (22.9%) were confirmed to have ototoxicity by audiometric criteria. The duration of treatment when ototoxicity was detected in the patients ranged 4-17 (Mean±SD; 9.4±3.4) weeks. Ototoxicity was detected in the audiometric low frequency ranges in 7 (43.8%) and at the high frequencies in 4 (25.0%) of the patients. Univariate analyses of clinical parameters found that age, underlying diabetes mellitus, deranged baseline PTAv >25dB HL, BMI on admission and retroviral status were significantly associated, while sex and previous drug regimen failure were not associated with ototoxicity. Multivariate adjusted logistic regression analyses, controlling for sex, revealed age (OR=1.068, p=0.018), BMI on admission (OR=0.673, p=0.012) and retroviral positivity (OR=8.822, p=0.014) of patients could significantly predict aminoglycoside-induced ototoxicity. Incidence of aminoglycoside-induced ototoxicity in DR Tb patients was 22.9%. The clinical predictors for ototoxicity were age

  6. Quality of Intensity Modulated Radiation Therapy Treatment Plans Using a {sup 60}Co Magnetic Resonance Image Guidance Radiation Therapy System

    SciTech Connect

    Wooten, H. Omar Green, Olga; Yang, Min; DeWees, Todd; Kashani, Rojano; Olsen, Jeff; Michalski, Jeff; Yang, Deshan; Tanderup, Kari; Hu, Yanle; Li, H. Harold; Mutic, Sasa

    2015-07-15

    Purpose: This work describes a commercial treatment planning system, its technical features, and its capabilities for creating {sup 60}Co intensity modulated radiation therapy (IMRT) treatment plans for a magnetic resonance image guidance radiation therapy (MR-IGRT) system. Methods and Materials: The ViewRay treatment planning system (Oakwood Village, OH) was used to create {sup 60}Co IMRT treatment plans for 33 cancer patients with disease in the abdominal, pelvic, thorax, and head and neck regions using physician-specified patient-specific target coverage and organ at risk (OAR) objectives. Backup plans using a third-party linear accelerator (linac)-based planning system were also created. Plans were evaluated by attending physicians and approved for treatment. The {sup 60}Co and linac plans were compared by evaluating conformity numbers (CN) with 100% and 95% of prescription reference doses and heterogeneity indices (HI) for planning target volumes (PTVs) and maximum, mean, and dose-volume histogram (DVH) values for OARs. Results: All {sup 60}Co IMRT plans achieved PTV coverage and OAR sparing that were similar to linac plans. PTV conformity for {sup 60}Co was within <1% and 3% of linac plans for 100% and 95% prescription reference isodoses, respectively, and heterogeneity was on average 4% greater. Comparisons of OAR mean dose showed generally better sparing with linac plans in the low-dose range <20 Gy, but comparable sparing for organs with mean doses >20 Gy. The mean doses for all {sup 60}Co plan OARs were within clinical tolerances. Conclusions: A commercial {sup 60}Co MR-IGRT device can produce highly conformal IMRT treatment plans similar in quality to linac IMRT for a variety of disease sites. Additional work is in progress to evaluate the clinical benefit of other novel features of this MR-IGRT system.

  7. Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Anal Cancer

    SciTech Connect

    Hodges, Joseph C.; Beg, Muhammad S.; Das, Prajnan; Meyer, Jeffrey

    2014-07-15

    Purpose: To compare the cost-effectiveness of intensity modulated radiation therapy (IMRT) and 3-dimensional conformal radiation therapy (3D-CRT) for anal cancer and determine disease, patient, and treatment parameters that influence the result. Methods and Materials: A Markov decision model was designed with the various disease states for the base case of a 65-year-old patient with anal cancer treated with either IMRT or 3D-CRT and concurrent chemotherapy. Health states accounting for rates of local failure, colostomy failure, treatment breaks, patient prognosis, acute and late toxicities, and the utility of toxicities were informed by existing literature and analyzed with deterministic and probabilistic sensitivity analysis. Results: In the base case, mean costs and quality-adjusted life expectancy in years (QALY) for IMRT and 3D-CRT were $32,291 (4.81) and $28,444 (4.78), respectively, resulting in an incremental cost-effectiveness ratio of $128,233/QALY for IMRT compared with 3D-CRT. Probabilistic sensitivity analysis found that IMRT was cost-effective in 22%, 47%, and 65% of iterations at willingness-to-pay thresholds of $50,000, $100,000, and $150,000 per QALY, respectively. Conclusions: In our base model, IMRT was a cost-ineffective strategy despite the reduced acute treatment toxicities and their associated costs of management. The model outcome was sensitive to variations in local and colostomy failure rates, as well as patient-reported utilities relating to acute toxicities.

  8. Intensity-modulated arc therapy to improve radiation dose delivery in the treatment of abdominal neuroblastoma.

    PubMed

    Gains, Jennifer E; Stacey, Christopher; Rosenberg, Ivan; Mandeville, Henry C; Chang, Yen-Ch'ing; D'Souza, Derek; Moroz, Veronica; Wheatley, Keith; Gaze, Mark N

    2013-03-01

    The standard European radiotherapy technique for children with neuroblastoma is a conventional parallel opposed pair. This frequently results in compromise on planning target volume coverage to stay within normal tissue tolerances. This study investigates the use of an intensity-modulated arc therapy (IMAT) technique to improve dose distribution and allow better protocol compliance. Among 20 previously treated patients, ten had received the full prescribed dose with conventional planning (protocol compliant) and ten had a compromise on planning target volume coverage (protocol noncompliant). All patients were replanned with IMAT. Dosimetric parameters of the conventional radiotherapy and IMAT were compared. The dose received by 98% of the planning target volume, homogeneity and conformity indices were all improved with IMAT (p < 0.001). IMAT would have enabled delivery of the full protocol dose in eight out of ten protocol-noncompliant patients. IMAT may improve outcomes through improved protocol compliance and better dose distributions.

  9. Improved highly accurate localized motion imaging for monitoring high-intensity focused ultrasound therapy

    NASA Astrophysics Data System (ADS)

    Qu, Xiaolei; Azuma, Takashi; Sugiyama, Ryusuke; Kanazawa, Kengo; Seki, Mika; Sasaki, Akira; Takeuchi, Hideki; Fujiwara, Keisuke; Itani, Kazunori; Tamano, Satoshi; Takagi, Shu; Sakuma, Ichiro; Matsumoto, Yoichiro

    2016-07-01

    Visualizing an area subjected to high-intensity focused ultrasound (HIFU) therapy is necessary for controlling the amount of HIFU exposure. One of the promising monitoring methods is localized motion imaging (LMI), which estimates coagulation length by detecting the change in stiffness. In this study, we improved the accuracy of our previous LMI by dynamic cross-correlation window (DCCW) and maximum vibration amount (MVA) methods. The DCCW method was used to increase the accuracy of estimating vibration amplitude, and the MVA method was employed to increase signal-noise ratio of the decrease ratio at the coagulated area. The qualitative comparison of results indicated that the two proposed methods could suppress the effect of noise. Regarding the results of the quantitative comparison, coagulation length was estimated with higher accuracy by the improved LMI method, and the root-mean-square error (RMSE) was reduced from 2.51 to 1.69 mm.

  10. Simple tool for prediction of parotid gland sparing in intensity-modulated radiation therapy

    SciTech Connect

    Gensheimer, Michael F.; Hummel-Kramer, Sharon M.; Cain, David; Quang, Tony S.

    2015-10-01

    Sparing one or both parotid glands is a key goal when planning head and neck cancer radiation treatment. If the planning target volume (PTV) overlaps one or both parotid glands substantially, it may not be possible to achieve adequate gland sparing. This finding results in physicians revising their PTV contours after an intensity-modulated radiation therapy (IMRT) plan has been run and reduces workflow efficiency. We devised a simple formula for predicting mean parotid gland dose from the overlap of the parotid gland and isotropically expanded PTV contours. We tested the tool using 44 patients from 2 institutions and found agreement between predicted and actual parotid gland doses (mean absolute error = 5.3 Gy). This simple method could increase treatment planning efficiency by improving the chance that the first plan presented to the physician will have optimal parotid gland sparing.

  11. Balancing control and simplicity: A variable aggregation method in intensity modulated radiation therapy planning*

    PubMed Central

    Süss, Philipp; Küfer, Karl-Heinz

    2008-01-01

    It is commonly believed that not all degrees of freedom are needed to produce good solutions for the treatment planning problem in intensity modulated radiation therapy (IMRT). However, typical methods to exploit this fact either increase the complexity of the optimization problem or are heuristic in nature. In this work we introduce a technique based on adaptively refining variable clusters to successively attain better treatment plans. The approach creates approximate solutions based on smaller models that may come arbitrarily close to the optimal solution. Although the method is illustrated using a specific treatment planning model, the components constituting the variable clustering and the adaptive refinement are independent of the particular optimization problem. PMID:19255600

  12. [Presence of the sacred in a critical moment: internment in an unit of intensive therapy].

    PubMed

    de Batista, Miranildes Abreu

    2004-01-01

    It is had as purpose understands the given meaning, for the patient, to the sacred object in a moment of internment in Unit of Intensive Therapy. Stands out forms of expression of the sacred in a critical instant in which the man in state of physical-emotional fragility, looks for answers transcendental front the anguish of the disease and of dying. The sacred is a trick of the religion through which the man tends taking refuge of the installed chaos. The presence of the sacred object, close to the patient, represents an event of immeasurable cultural meaning, being revealed in a supra-natural entail of which exhales hope, safety, help, comfort and, even, company.

  13. PRESAGE® as a new calibration method for high intensity focused ultrasound therapy

    NASA Astrophysics Data System (ADS)

    Costa, M.; McErlean, C.; Rivens, I.; Adamovics, J.; Leach, M. O.; ter Haar, G.; Doran, S. J.

    2015-01-01

    High Intensity Focused ultrasound (HIFU) is a non-invasive cancer therapy that makes use of the mainly thermal effects of ultrasound to destroy tissue. In order to achieve reliable treatment planning, it is necessary to characterise the ultrasound source (transducer) and to understand how the wave propagates in tissue and the energy deposition in the focal region. This novel exploratory study investigated how HIFU affects PRESAGE®, an optical phantom used for radiotherapy dosimetry, which is potentially a rapid method of calibrating the transducer. Samples, of two different formulations, were exposed to focused ultrasound and imaged using Optical Computed Tomography. First results showed that, PRESAGE® changes colour on ultrasound exposure (darker green regions were observed) with the alterations being related to the acoustic power and sample composition. Future work will involve quantification of these alterations and understanding how to relate them to the mechanisms of action of HIFU.

  14. Matching Intensity-Modulated Radiation Therapy to an Anterior Low Neck Field

    SciTech Connect

    Amdur, Robert J. Liu, Chihray; Li, Jonathan; Mendenhall, William; Hinerman, Russell

    2007-10-01

    When using intensity-modulated radiation therapy (IMRT) to treat head and neck cancer with the primary site above the level of the larynx, there are two basic options for the low neck lymphatics: to treat the entire neck with IMRT, or to match the IMRT plan to a conventional anterior 'low neck' field. In view of the potential advantages of using a conventional low neck field, it is important to look for ways to minimize or manage the problems of matching IMRT to a conventional radiotherapy field. Treating the low neck with a single anterior field and the standard larynx block decreases the dose to the larynx and often results in a superior IMRT plan at the primary site. The purpose of this article is to review the most applicable studies and to discuss our experience with implementing a technique that involves moving the position of the superior border of the low neck field several times during a single treatment fraction.

  15. Extensive Variability in Vasoactive Agent Therapy: A Nationwide Survey in Chinese Intensive Care Units

    PubMed Central

    Pei, Xian-Bo; Ma, Peng-Lin; Li, Jian-Guo; Du, Zhao-Hui; Zhou, Qing; Lu, Zhang-Hong; Yun, Luo; Hu, Bo

    2015-01-01

    Background: Inconsistencies in the use of the vasoactive agent therapy to treat shock are found in previous studies. A descriptive study was proposed to investigate current use of vasoactive agents for patients with shock in Chinese intensive care settings. Methods: A nationwide survey of physicians was conducted from August 17 to December 30, 2012. Physicians were asked to complete a questionnaire which focused on the selection of vasoactive agents, management in the use of vasopressor/inotropic therapy, monitoring protocols when using these agents, and demographic characteristics. Results: The response rate was 65.1% with physicians returning 586 valid questionnaires. Norepinephrine was the first choice of a vasopressor used to treat septic shock by 70.8% of respondents; 73.4% of respondents favored dopamine for hypovolemic shock; and 68.3% of respondents preferred dopamine for cardiogenic shock. Dobutamine was selected by 84.1%, 64.5%, and 60.6% of respondents for septic, hypovolemic, and cardiogenic shock, respectively. Vasodilator agents were prescribed by physicians in the management of cardiogenic shock (67.1%) rather than for septic (32.3%) and hypovolemic shock (6.5%). A significant number of physicians working in teaching hospitals were using vasoactive agents in an appropriate manner when compared to physicians in nonteaching hospitals. Conclusions: Vasoactive agent use for treatment of shock is inconsistent according to self-report by Chinese intensive care physicians; however, the variation in use depends upon the form of shock being treated and the type of hospital; thus, corresponding educational programs about vasoactive agent use for shock management should be considered. PMID:25881592

  16. Severe hypoglycemia while on intensive insulin therapy is not an independent predictor of death after trauma.

    PubMed

    Mowery, Nathan T; Guillamondegui, Oscar D; Gunter, Oliver L; Diaz, Jose J; Collier, Bryan R; Dossett, Lesly A; Dortch, Marcus J; May, Addison K

    2010-02-01

    Fear of the adverse effects of hypoglycemia has limited the widespread application of intensive insulin therapy (goal, 80-110 mg/dL) in the trauma population. We hypothesized that severe hypoglycemia (SH; intensive insulin therapy from November 2005 to May 2008 was performed. The primary outcomes of interest were any episode of SH (<40 mg/dL) and all-cause inhospital mortality. Multivariate logistic regression was used to estimate the independent relationship between hypoglycemia and death. : Fifty-seven thousand two hundred eighty-four data entries (1,824 patients) from the euglycemia protocol were analyzed (mortality = 16.0%). Median glucose was 119 mg/dL, with 43% of values between 80 mg/dL and 110 mg/dL, 81% between 80 mg/dL and 150 mg/dL, and 0.3% <40 mg/dL. There were 126 severe hypoglycemic episodes in 111 patients (6.1% of the patients). Multivariate logistic regression revealed that SH was not independently associated with death after adjusting for other known risk factors (odds ratio, 1.244; 95% confidence interval, 0.853-1.816; p = 0.257). Hypoglycemia may be an unavoidable byproduct of tight glucose control with 6.1% of the patients experiencing a severe hypoglycemic event (<40 mg/dL). Hypoglycemia is not an independent predictor of death. Hypoglycemia is a statistical probability of time spent on protocol rather than an event leading to death. These data suggest that lower glucose ranges should be targeted in the trauma population without fear of hypoglycemia's adverse effect on mortality.

  17. Intensity Modulated Radiation Therapy for Primary Soft Tissue Sarcoma of the Extremity: Preliminary Results

    SciTech Connect

    Alektiar, Kaled M. . E-mail: alektiak@mskcc.org; Hong, Linda; Brennan, Murray F.; Della-Biancia, Cesar; Singer, Samuel

    2007-06-01

    Purpose: To report preliminary results on using intensity modulated radiation therapy (IMRT) as an adjuvant treatment in primary soft tissue sarcoma (STS) of the extremity. Methods and Materials: Between February 2002 and March 2005, 31 adult patients with primary STS of the extremity were treated with surgery and adjuvant IMRT. Tumor size was >10 cm in 74% of patients and grade was high in 77%. Preoperative IMRT was given to 7 patients (50 Gy) and postoperative IMRT (median dose, 63 Gy) was given to 24 patients. Complete gross resection including periosteal stripping or bone resection was required in 10, and neurolysis or nerve resection in 20. The margins were positive or within 1 mm in 17. Complications from surgery and radiation therapy (RT) were assessed using the Common Terminology Criteria for Adverse Events grading system. Results: Median follow-up time was 23 months. Grade 1 RT dermatitis developed in 71% of patients, Grade 2 in 16%, and Grade 3 in 10%. Infectious wound complications developed in 13% and noninfectious complications in 10%. Two patients (6.4%) developed fractures. Grade 1 neuropathy developed in 28% of patients and Grade 2 in 5%. The rates of Grade 1 and 2 joint stiffness were each 19%. Grade 1 edema was observed in 19% of patients and Grade 2 in 13%. The 2-year local control, distant control, and overall survival were 95%, 65%, and 81%, respectively. Conclusion: Intensity modulated RT appears to provide excellent local control in a difficult group of high-risk patients. The morbidity profile is also favorable, but longer follow-up is needed to confirm the results from this study.

  18. Robust Intensity Modulated Proton Therapy (IMPT) Increases Estimated Clinical Benefit in Head and Neck Cancer Patients

    PubMed Central

    van Dijk, Lisanne V.; Steenbakkers, Roel J. H. M.; ten Haken, Bennie; van der Laan, Hans Paul; van ‘t Veld, Aart A.; Langendijk, Johannes A.; Korevaar, Erik W.

    2016-01-01

    Purpose To compare the clinical benefit of robust optimized Intensity Modulated Proton Therapy (minimax IMPT) with current photon Intensity Modulated Radiation Therapy (IMRT) and PTV-based IMPT for head and neck cancer (HNC) patients. The clinical benefit is quantified in terms of both Normal Tissue Complication Probability (NTCP) and target coverage in the case of setup and range errors. Methods and Materials For 10 HNC patients, PTV-based IMRT (7 fields), minimax and PTV-based IMPT (2, 3, 4, 5 and 7 fields) plans were tested on robustness. Robust optimized plans differed from PTV-based plans in that they target the CTV and penalize possible error scenarios, instead of using the static isotropic CTV-PTV margin. Perturbed dose distributions of all plans were acquired by simulating in total 8060 setup (±3.5 mm) and range error (±3%) combinations. NTCP models for xerostomia and dysphagia were used to predict the clinical benefit of IMPT versus IMRT. Results The robustness criterion was met in the IMRT and minimax IMPT plans in all error scenarios, but this was only the case in 1 of 40 PTV-based IMPT plans. Seven (out of 10) patients had relatively large NTCP reductions in minimax IMPT plans compared to IMRT. For these patients, xerostomia and dysphagia NTCP values were reduced by 17.0% (95% CI; 13.0–21.1) and 8.1% (95% CI; 4.9–11.2) on average with minimax IMPT. Increasing the number of fields did not contribute to plan robustness, but improved organ sparing. Conclusions The estimated clinical benefit in terms of NTCP of robust optimized (minimax) IMPT is greater than that of IMRT and PTV-based IMPT in HNC patients. Furthermore, the target coverage of minimax IMPT plans in the presence of errors was comparable to IMRT plans. PMID:27030987

  19. The effect of massage therapy on occupational stress of Intensive Care Unit nurses

    PubMed Central

    Nazari, Fateme; Mirzamohamadi, Mojtaba; Yousefi, Hojatollah

    2015-01-01

    Background: One of the main causes of stress in the lives of people is their jobs. Occupational stress is causing a wide range of significant issues in health and community services. Nursing is the most stressful profession in the health services. Massage therapy is one way of coping with stress. This study was conducted to determine the effect of massage therapy on stress in nurses. Materials and Methods: This study was a clinical trial on 66 male and female nurses working in intensive care units (dialysis, ICU, and CCU) of Isfahan University of Medical Sciences, Iran, in 2013. Participants were selected according to the aims and inclusion criteria of the study. Then, they were randomly divided into experimental and control groups. The Occupational Stress Inventory (OSI) (Osipow and Spokane, 1987) was completed by participants of the two groups before, immediately after, and 2 weeks after the intervention. General Swedish massage was performed on participants of the experimental group for 25 min in each session, twice a week for 4 weeks. Data were analyzed by descriptive and inferential statistics [Chi-square, t-test, and repeated measures analysis of variance (ANOVA)] using SPSS software. Results: Results showed that the difference in overall mean occupation stress scores between experimental and control groups 2 weeks after the intervention was significant (P < 0.001). Conclusions: According to the results, it is recommended that massage, as a valuable noninvasive method, be used for nurses in intensive care units to reduce their stress, promote mental health, and prevent the decrease in quality of nursing work life. PMID:26257809

  20. A comparison of three optimization algorithms for intensity modulated radiation therapy.

    PubMed

    Pflugfelder, Daniel; Wilkens, Jan J; Nill, Simeon; Oelfke, Uwe

    2008-01-01

    In intensity modulated treatment techniques, the modulation of each treatment field is obtained using an optimization algorithm. Multiple optimization algorithms have been proposed in the literature, e.g. steepest descent, conjugate gradient, quasi-Newton methods to name a few. The standard optimization algorithm in our in-house inverse planning tool KonRad is a quasi-Newton algorithm. Although this algorithm yields good results, it also has some drawbacks. Thus we implemented an improved optimization algorithm based on the limited-memory Broyden-Fletcher-Goldfarb-Shanno (L-BFGS) routine. In this paper the improved optimization algorithm is described. To compare the two algorithms, several treatment plans are optimized using both algorithms. This included photon (IMRT) as well as proton (IMPT) intensity modulated therapy treatment plans. To present the results in a larger context the widely used conjugate gradient algorithm was also included into this comparison. On average, the improved optimization algorithm was six times faster to reach the same objective function value. However, it resulted not only in an acceleration of the optimization. Due to the faster convergence, the improved optimization algorithm usually terminates the optimization process at a lower objective function value. The average of the observed improvement in the objective function value was 37%. This improvement is clearly visible in the corresponding dose-volume-histograms. The benefit of the improved optimization algorithm is particularly pronounced in proton therapy plans. The conjugate gradient algorithm ranked in between the other two algorithms with an average speedup factor of two and an average improvement of the objective function value of 30%.

  1. [Is intensive functional insulin therapy the method of choice in newly diagnosed type-1 diabetes mellitus?].

    PubMed

    Araszkiewicz, Aleksandra; Zozulińska, Dorota; Trepińska, Magdalena; Wierusz-Wysocka, Bogna

    2004-11-01

    The aim of our study was a prospective evaluation of type 1 diabetic patients treated with intensive insulin therapy. We recruited 100 patients (62 males and 38 females) aged 24.3+/-6.2 years with newly diagnosed type 1 diabetes. The mean observation period was 5.2+/-1.5 years. Parameters of diabetes metabolic balance, occurrence of chronic complications and patients' knowledge about the disease and the methods of its treatment were evaluated. 68% of the patients controlled their glycaemia regularly before main meals and 53% of them had a diabetic diary. In the knowledge test 20% of the subjects reached < or = 11 points, 62% 11-17 points and 18% > 17 points (mean 14.4+/-3.2 points of maximal 20 to achieve). The mean result in the questionnaire of knowledge about the disease was 28.1+/-4.9 points. Fasting glycaemia was 7.2+/-3.4 mmol/l, 2h postprandial glycaemia 9.4+/-3.6 mmol/l, HbA1c 7.5+/-1.4%, the mean C-peptide level 0.9+/-0.4 ng/ml and the number of hypoglycaemic episodes was 6/individual/month. We observed a statistically significant correlation between the level of patients' knowledge and HbA1c (r=-0.31, p<0.05). Retinopathy and nephropathy were detected in 8 (9%) and 6 (6.8%) subjects respectively. The risk of microangiopathy was connected with low knowledge (RR: 5.67; 95% CI: 2.02-15.82, p<0.0002). The study confirms the crucial role of intensive insulin therapy and systematic patients' education concerning the disease in maintaining a good metabolic control and thus reducing the risk of diabetic vascular complications.

  2. Intensity-modulated radiation therapy, protons, and the risk of second cancers

    SciTech Connect

    Hall, Eric J. . E-mail: ejh1@columbia.edu

    2006-05-01

    Intensity-modulated radiation therapy (IMRT) allows dose to be concentrated in the tumor volume while sparing normal tissues. However, the downside to IMRT is the potential to increase the number of radiation-induced second cancers. The reasons for this potential are more monitor units and, therefore, a larger total-body dose because of leakage radiation and, because IMRT involves more fields, a bigger volume of normal tissue is exposed to lower radiation doses. Intensity-modulated radiation therapy may double the incidence of solid cancers in long-term survivors. This outcome may be acceptable in older patients if balanced by an improvement in local tumor control and reduced acute toxicity. On the other hand, the incidence of second cancers is much higher in children, so that doubling it may not be acceptable. IMRT represents a special case for children for three reasons. First, children are more sensitive to radiation-induced cancer than are adults. Second, radiation scattered from the treatment volume is more important in the small body of the child. Third, the question of genetic susceptibility arises because many childhood cancers involve a germline mutation. The levels of leakage radiation in current Linacs are not inevitable. Leakage can be reduced but at substantial cost. An alternative strategy is to replace X-rays with protons. However, this change is only an advantage if the proton machine employs a pencil scanning beam. Many proton facilities use passive modulation to produce a field of sufficient size, but the use of a scattering foil produces neutrons, which results in an effective dose to the patient higher than that characteristic of IMRT. The benefit of protons is only achieved if a scanning beam is used in which the doses are 10 times lower than with IMRT.

  3. [The influence of intensive insulin therapy on hemodynamics in patients with septic shock].

    PubMed

    Dong, Shi-min; Qin, Yan-jun; Gao, Yu-fang

    2009-05-01

    To elucidate effects of intensive insulin therapy and target glucose control on hemodynamics and cardiac function in patients with septic shock. Twenty-seven patients of septic shock with myocardial depression were divided into routine group (14 cases, level of blood glucose was 4.1 to 6.1 mmol/L) and target group (13 cases, level of blood glucose was 6.2 to 8.3 mmol/L). Hemodynamics and cardiac function parameters were obtained via pulmonary artery catheter after 48 hours. Mean blood glucose level in target group was lower than that in routine group [(6.0+/-1.5) mmol/L vs. (8.2+/-1.9) mmol/L, P<0.05], with dosage of insulin infusion in target group increased as compared with that of routine group [(10.3+/-3.7) U/h vs. (7.5+/-3.0) U/h, P<0.05]. Furthermore, oxygenation index (PaO(2)/FiO(2)), stroke volume index (SVI), cardiac index (CI) and oxygen delivery index (DO(2)I) were increased 20.2%, 23.3%, 15.1% and 11.7%, respectively (all P<0.05). On the other hands, there was no significant difference between target and routine group in mean artery pressure, acute physiology and chronic health evaluation II (APACHEII) score, blood lactic acid (all P>0.05), although the incidence of severe hypoglycemia was higher in target group than the routine group (38.5% vs. 28.6%, P>0.05). Intensive insulin therapy and blood glucose control may improve hemodynamic status and enhance cardiac function in patients with septic shock and myocardial depression.

  4. P13.25A RADIOBIOLOGICAL COMPARISON BETWEEN THE INVERSE INTENSITY MODULATED RADIATION THERAPY AND THE FIELD IN FIELD INTENSITY MODULATED RADIATION THERAPY FOR THE TREATMENT OF GLIOBLASTOMA

    PubMed Central

    Yazici, A.; Dirican, B.; Kara, E.

    2014-01-01

    For critical structures the use of maximum or mean dose limits in the intensity modulated radiation therapy (IMRT) optimization is not very meaningful. The dose-volume limits and equivalent uniform dose (EUD) which is defined as the uniform dose that would lead to the same effect as the given non-uniform dose in as particular organ are combined to analyze the volume effect. The normal tissue complication probability (NTCP) is a predictor of radiobiological effect for organs at risk (OAR). The calculation of the NTCP is based on the DVH which is generated by the treatment planning system after calculation of the 3D dose distribution. Uniform EUD irradiation of an OAR results in the same NTCP as the original non-homogeneous distribution. The NTCP equation is therefore represented as a function of EUD. The inverse equation expresses EUD as a function of NTCP. Expressing NTCP in terms of EUD represents a step toward simplifying the conceptual framework for modeling probability of expected complications. The aim of this study is to compare radiobiological effects between the fif IMRT and inverse IMRT for treatment of Glioblastoma (GBM) using the equivalent uniform dose (EUD) and normal tissue complication probability (NTCP). Five representative patients treated with definitive radiation using IMRT at our clinic in the last two year were selected for treatment planning study. Criteria for inclusion were glioblastoma . The normal tissues (Organ at Risk, OaR) contoured included brain-stem, optic chiasm, optic nerves, right-left cohclea and whole brain. Brain was defined as total brain tissue minus the PTV. Two different radiation therapy techniques; inverse IMRT and FiF IMRT treatment plans were optimised with the prescription dose 60 Gy/30 fractions. All those calculations and IMRT optimizations were performed using the Prowess Panther DAQ TPS with 6 MV,Siemens Artiste, MLC with 160 leaves and evaluated by using EUD and NTCP models. In the present study, target dose

  5. Multifield Optimization Intensity Modulated Proton Therapy for Head and Neck Tumors: A Translation to Practice

    SciTech Connect

    Frank, Steven J.; Cox, James D.; Gillin, Michael; Mohan, Radhe; Garden, Adam S.; Rosenthal, David I.; Gunn, G. Brandon; Weber, Randal S.; Kies, Merrill S.; Lewin, Jan S.; Munsell, Mark F.; Palmer, Matthew B.; Sahoo, Narayan; Zhang, Xiaodong; Liu, Wei; Zhu, X. Ronald

    2014-07-15

    Background: We report the first clinical experience and toxicity of multifield optimization (MFO) intensity modulated proton therapy (IMPT) for patients with head and neck tumors. Methods and Materials: Fifteen consecutive patients with head and neck cancer underwent MFO-IMPT with active scanning beam proton therapy. Patients with squamous cell carcinoma (SCC) had comprehensive treatment extending from the base of the skull to the clavicle. The doses for chemoradiation therapy and radiation therapy alone were 70 Gy and 66 Gy, respectively. The robustness of each treatment plan was also analyzed to evaluate sensitivity to uncertainties associated with variations in patient setup and the effect of uncertainties with proton beam range in patients. Proton beam energies during treatment ranged from 72.5 to 221.8 MeV. Spot sizes varied depending on the beam energy and depth of the target, and the scanning nozzle delivered the spot scanning treatment “spot by spot” and “layer by layer.” Results: Ten patients presented with SCC and 5 with adenoid cystic carcinoma. All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks and no hospitalizations. There were no treatment-related deaths, and with a median follow-up time of 28 months (range, 20-35 months), the overall clinical complete response rate was 93.3% (95% confidence interval, 68.1%-99.8%). Xerostomia occurred in all 15 patients as follows: grade 1 in 10 patients, grade 2 in 4 patients, and grade 3 in 1 patient. Mucositis within the planning target volumes was seen during the treatment of all patients: grade 1 in 1 patient, grade 2 in 8 patients, and grade 3 in 6 patients. No patient experienced grade 2 or higher anterior oral mucositis. Conclusions: To our knowledge, this is the first clinical report of MFO-IMPT for head and neck tumors. Early clinical outcomes are encouraging and warrant further investigation of proton therapy in prospective clinical trials.

  6. High remission and low relapse with prolonged intensive DMARD therapy in rheumatoid arthritis (PRINT)

    PubMed Central

    Li, Ru; Zhao, Jin-Xia; Su, Yin; He, Jing; Chen, Li-Na; Gu, Fei; Zhao, Cheng; Deng, Xue-Rong; Zhou, Wei; Hao, Yan-Jie; Xue, Yu; Liu, Hua-Xiang; Zhao, Yi; Zou, Qing-Hua; Liu, Xiang-Yuan; Zhu, Ping; Sun, Ling-Yun; Zhang, Zhuo-Li; Zou, He-Jian; Li, Xing-Fu; Liu, Yi; Fang, Yong-Fei; Keystone, Edward; McInnes, Iain B.; Li, Zhan-Guo

    2016-01-01

    Abstract Objectives: To determine whether prolonged intensive disease-modifying antirheumatic drug (DMARD) treatment (PRINT) leads to high remission and low relapse rates in patients with severe rheumatoid arthritis (RA). Methods: In this multicenter, randomized and parallel treatment trial, 346 patients with active RA (disease activity score (28 joints) [DAS28] (erythrocyte sedimentation rate [ESR]) > 5.1) were enrolled from 9 centers. In phase 1, patients received intensive treatment with methotrexate, leflunomide, and hydroxychloroquine, up to 36 weeks, until remission (DAS28 ≤ 2.6) or a low disease activity (2.6 < DAS28 ≤ 3.2) was achieved. In phase 2, patients achieving remission or low disease activity were followed up with randomization to 1 of 2 step-down protocols: leflunomide plus hydroxychloroquine combination or leflunomide monotherapy. The primary endpoints were good European League Against Rheumatism (EULAR) response (DAS28 (ESR) < 3.2 and a decrease of DAS28 by at least 1.2) during the intensive treatment and the disease state retention rate during step-down maintenance treatment. Predictors of a good EULAR response in the intensive treatment period and disease flare in the maintenance period were sought. Results: A good EULAR response was achieved in 18.7%, 36.9%, and 54.1% of patients at 12, 24, and 36 weeks, respectively. By 36 weeks, 75.4% of patients achieved good and moderate EULAR responses. Compared with those achieving low disease activity and a high health assessment questionnaire (HAQ > 0.5), patients achieving remission (DAS28 ≤ 2.6) and low HAQ (≤ 0.5) had a significantly higher retention rate when tapering the DMARDs treatment (P = 0.046 and P = 0.01, respectively). There was no advantage on tapering to combination rather than monotherapy. Conclusions: Remission was achieved in a proportion of patients with RA receiving prolonged intensive DMARD therapy. Low disease activity at the start of disease taper leads to less subsequent

  7. Patient and Family Perceptions of Physical Therapy in the Medical Intensive Care Unit

    PubMed Central

    Sottile, Peter D; Nordon-Craft, Amy; Malone, Daniel; Schenkman, Margaret; Moss, Marc

    2015-01-01

    Purpose Patient and family member perceptions of physical therapy (PT) in the intensive care unit and the factors that influence their degree of satisfaction have not been described. Methods A panel of experts developed a questionnaire that assessed patient and family perceptions of PT. Critically ill patients and their family members were asked to complete the survey. Patient and family member scores were compared and stratified by age, gender, and mechanical ventilation for greater than 14 days compared to 14 days or less. Results A total of 55 patients and 49 family members completed the survey. Patients and family members reported that PT was necessary and beneficial to recovery, despite associating PT with difficulty, exertion, and discomfort. Patient perceptions were similar regardless of age or gender. Family members underestimated a patient's enjoyment of PT (p=0.03). For individuals who required prolonged mechanical ventilation (>14 days), patients reported that PT was more difficult (p=0.03), less enjoyable (p=0.049), and family members reported PT as causing greater discomfort (p=0.005). Additionally, family members of patients who required prolonged mechanical ventilation felt that PT was less beneficial (p=0.01). Conclusions Physical therapy is perceived as necessary and beneficial to recovery by critically ill patients and family members. PMID:26038155

  8. Pulsed low-intensity ultrasound therapy for chronic lateral epicondylitis: a randomized controlled trial.

    PubMed

    D'Vaz, A P; Ostor, A J K; Speed, C A; Jenner, J R; Bradley, M; Prevost, A T; Hazleman, B L

    2006-05-01

    Pulsed low-intensity ultrasound therapy (LIUS) has been found to be beneficial in accelerating fracture healing and has produced positive results in animal tendon repair. In the light of this we undertook a randomized, double-blind, placebo controlled trial to assess the effectiveness of LIUS vs placebo therapy daily for 12 weeks in patients with chronic lateral epicondylitis (LE). Patients with LE of at least 6 weeks' duration were recruited from general practice, physiotherapy and rheumatology clinics, and had to have failed at least one first-line treatment including non steroidal anti-inflammatory drugs (NSAIDs) and corticosteroid injection. Participants were assigned either active LIUS or placebo. Treatment was self-administered daily for 20 min over a 12-week period. The primary end-point was a 50% improvement from baseline in elbow pain measured at 12 weeks using a patient-completed visual analogue scale. Fifty-five subjects aged 18-80 were recruited over a 9-month period. In the active group 64% (16/25) achieved at least 50% improvement from baseline in elbow pain at 12 weeks compared with 57% (13/23) in the placebo group (difference of 7%; 95% confidence interval -20 to 35%). However, this was not statistically significant (chi(2) = 0.28, P = 0.60). In this study LIUS was no more effective for a large treatment effect than placebo for recalcitrant LE. This is in keeping with other interventional studies for the condition.

  9. [Vestibular disorders and nausea during head and neck intensity-modulated radiation therapy].

    PubMed

    Berta, É; Righini, C A; Chamorey, E; Villa, J; Atallah, I; Reyt, É; Coffre, A; Schmerber, S

    2016-06-01

    We studied whether there is a relationship between nausea and vestibular disorders in patients treated with intensity modulated radiation therapy (IMRT) for head and neck cancer. We performed a prospective single-centre study that enrolled 31 patients. A videonystagmography was carried out before and within 15 days after radiation therapy for each patient. Nausea was assessed at baseline, every week, and at the post-radiotherapy videonystagmography visit. Twenty-six patients had benefited from a complete interpretable videonystagmography. For 14 of these patients vestibular damage was diagnosed post-radiotherapy. During irradiation, six patients felt nauseous, but without dizziness. In univariate analysis, we found a relationship statistically significant between the average dose received by the vestibules and vestibular disorder videonystagmography (P=0.001, odds ratio [OR]: 1.08 [1.025-.138]), but there was no relationship between vestibular disorder videonystagmography and nausea (P=0.701). Irradiation of the vestibular system during IMRT does not seem to explain the nausea. Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.