This document provides an introduction and methods section for a meta-analysis comparing the effectiveness of three treatments for myelodysplastic syndrome (MDS): epigenetic therapy, chemotherapy, and bone marrow transplant. The methods describe how studies were identified and selected for each treatment from various databases. Key criteria for study inclusion were described, such as median patient age, year of publication, and reporting of results in terms of remission rates. The selected studies for each treatment were then compiled into tables to analyze and compare the treatments' effectiveness based on outcomes like complete remission rates.
This document provides guidance on how to display data in summaries, tables, and graphs for research publications and presentations. It discusses which types of data are qualitative versus quantitative, and how to present numbers, percentages, and measures of central tendency and dispersion. Recommendations are given for constructing tables, such as ordering rows and columns clearly and minimizing lines. Guidelines for different types of graphs are outlined, including bar charts, pie charts, and line graphs. The document emphasizes principles from Tufte for maximizing information while minimizing ink in data displays.
This meta-analysis examined 17 studies involving 9,454 subjects to determine the prevalence of treatment need for temporomandibular disorders (TMD) in adult nonpatient populations. The analysis found that the prevalence of TMD treatment need was estimated to be 15.6% according to the fixed effect model and 16.2% according to the random effects model. Criteria used to estimate treatment need and the location of the study strongly influenced the estimates. Estimates based on clinical TMD signs were higher than those based on self-reported symptoms. Younger subjects aged 19-45 had higher estimates of treatment need than older subjects aged 46 and over. The treatment need for TMD in the general adult population is substantial and
This study evaluated the use of sirolimus, an mTOR inhibitor, in 4 patients with diffuse hyperinsulinemic hypoglycemia that was unresponsive to standard treatments with diazoxide and octreotide. Patients received sirolimus with dose adjustments to achieve target serum levels. Glycemic control improved in all patients after starting sirolimus. The study suggests mTOR inhibitors may provide an alternative treatment option for severe hyperinsulinemic hypoglycemia unresponsive to other therapies, but larger and longer-term studies are still needed to fully evaluate efficacy and safety.
What is the best evidence in medicine?Samir Haffar
This document discusses the hierarchy of evidence and types of medical studies used to evaluate evidence. It begins by defining evidence-based medicine as integrating the best research evidence, clinical expertise, and patient values. It then outlines the different types of studies from case reports and case series up to systematic reviews and meta-analyses. Randomized controlled trials are considered the gold standard but all study types have strengths and limitations. The document emphasizes finding the highest quality evidence available and assessing it critically to inform clinical decision making.
Benefits os Statins in Elderly Subjects Without Established Cardiovascular Di...Rodrigo Vargas Zapana
Statins significantly reduced the risk of myocardial infarction by 39.4% and the risk of stroke by 23.8% in elderly subjects without established cardiovascular disease. However, statins did not significantly reduce the risk of all-cause mortality or cardiovascular mortality. New cancer onset was also not significantly different between the statin-treated and placebo groups. The meta-analysis included 8 randomized controlled trials with a total of 24,674 elderly subjects who were followed for an average of 3.5 years.
This document summarizes two studies that raised questions about the risks and benefits of testosterone therapy:
1. A retrospective study found that male veterans with low testosterone who received testosterone therapy had a higher risk of heart attack, stroke, or death compared to those not receiving therapy, even after adjusting for potential confounding factors.
2. A randomized trial found that adding testosterone to optimized sildenafil therapy for erectile dysfunction provided no additional improvement in erectile function compared to sildenafil alone.
Together these studies highlight the need for more research on the long-term risks and benefits of testosterone therapy, as current understanding is limited despite its increasing use.
The utility of “blind” 131I treatments for differentiated thyroid cancer: an...Michael
This document reviews literature on the use of 131I "blind" therapy, which is 131I treatment for differentiated thyroid cancer patients who have a positive thyroglobulin level and negative radioiodine whole body scan. It summarizes several studies that evaluated treatment outcomes based on changes in thyroglobulin levels post-therapy. The studies found response rates varied, with partial response in about 60% of treated patients and complete response in only 3%, compared to 44.6% and 5.4% respectively in untreated patients. However, the document concludes that the current literature does not resolve the controversy due to limitations like small sample sizes and lack of standardization in evaluating outcomes. More comprehensive prospective studies are needed to properly assess the
This study analyzed bleeding events among 5,170 patients from the CHANCE trial who received dual antiplatelet therapy (clopidogrel plus aspirin) or aspirin alone for minor stroke or transient ischemic attack. A total of 101 bleeding events occurred, with no significant difference in rates between the treatment groups. However, patients with minor strokes had a higher risk of bleeding than those with transient ischemic attacks. Being elderly, male, and having a history of aspirin or proton pump inhibitor use were associated with greater bleeding risk, while higher body mass index was protective against bleeding.
This document provides guidance on how to display data in summaries, tables, and graphs for research publications and presentations. It discusses which types of data are qualitative versus quantitative, and how to present numbers, percentages, and measures of central tendency and dispersion. Recommendations are given for constructing tables, such as ordering rows and columns clearly and minimizing lines. Guidelines for different types of graphs are outlined, including bar charts, pie charts, and line graphs. The document emphasizes principles from Tufte for maximizing information while minimizing ink in data displays.
This meta-analysis examined 17 studies involving 9,454 subjects to determine the prevalence of treatment need for temporomandibular disorders (TMD) in adult nonpatient populations. The analysis found that the prevalence of TMD treatment need was estimated to be 15.6% according to the fixed effect model and 16.2% according to the random effects model. Criteria used to estimate treatment need and the location of the study strongly influenced the estimates. Estimates based on clinical TMD signs were higher than those based on self-reported symptoms. Younger subjects aged 19-45 had higher estimates of treatment need than older subjects aged 46 and over. The treatment need for TMD in the general adult population is substantial and
This study evaluated the use of sirolimus, an mTOR inhibitor, in 4 patients with diffuse hyperinsulinemic hypoglycemia that was unresponsive to standard treatments with diazoxide and octreotide. Patients received sirolimus with dose adjustments to achieve target serum levels. Glycemic control improved in all patients after starting sirolimus. The study suggests mTOR inhibitors may provide an alternative treatment option for severe hyperinsulinemic hypoglycemia unresponsive to other therapies, but larger and longer-term studies are still needed to fully evaluate efficacy and safety.
What is the best evidence in medicine?Samir Haffar
This document discusses the hierarchy of evidence and types of medical studies used to evaluate evidence. It begins by defining evidence-based medicine as integrating the best research evidence, clinical expertise, and patient values. It then outlines the different types of studies from case reports and case series up to systematic reviews and meta-analyses. Randomized controlled trials are considered the gold standard but all study types have strengths and limitations. The document emphasizes finding the highest quality evidence available and assessing it critically to inform clinical decision making.
Benefits os Statins in Elderly Subjects Without Established Cardiovascular Di...Rodrigo Vargas Zapana
Statins significantly reduced the risk of myocardial infarction by 39.4% and the risk of stroke by 23.8% in elderly subjects without established cardiovascular disease. However, statins did not significantly reduce the risk of all-cause mortality or cardiovascular mortality. New cancer onset was also not significantly different between the statin-treated and placebo groups. The meta-analysis included 8 randomized controlled trials with a total of 24,674 elderly subjects who were followed for an average of 3.5 years.
This document summarizes two studies that raised questions about the risks and benefits of testosterone therapy:
1. A retrospective study found that male veterans with low testosterone who received testosterone therapy had a higher risk of heart attack, stroke, or death compared to those not receiving therapy, even after adjusting for potential confounding factors.
2. A randomized trial found that adding testosterone to optimized sildenafil therapy for erectile dysfunction provided no additional improvement in erectile function compared to sildenafil alone.
Together these studies highlight the need for more research on the long-term risks and benefits of testosterone therapy, as current understanding is limited despite its increasing use.
The utility of “blind” 131I treatments for differentiated thyroid cancer: an...Michael
This document reviews literature on the use of 131I "blind" therapy, which is 131I treatment for differentiated thyroid cancer patients who have a positive thyroglobulin level and negative radioiodine whole body scan. It summarizes several studies that evaluated treatment outcomes based on changes in thyroglobulin levels post-therapy. The studies found response rates varied, with partial response in about 60% of treated patients and complete response in only 3%, compared to 44.6% and 5.4% respectively in untreated patients. However, the document concludes that the current literature does not resolve the controversy due to limitations like small sample sizes and lack of standardization in evaluating outcomes. More comprehensive prospective studies are needed to properly assess the
This study analyzed bleeding events among 5,170 patients from the CHANCE trial who received dual antiplatelet therapy (clopidogrel plus aspirin) or aspirin alone for minor stroke or transient ischemic attack. A total of 101 bleeding events occurred, with no significant difference in rates between the treatment groups. However, patients with minor strokes had a higher risk of bleeding than those with transient ischemic attacks. Being elderly, male, and having a history of aspirin or proton pump inhibitor use were associated with greater bleeding risk, while higher body mass index was protective against bleeding.
Study of the distribution and determinants of
health-related states or events in specified populations and the application of this study to control health problems.
John M. Last, Dictionary of Epidemiology
The survey analyzed treatment patterns for multiple myeloma in Germany between 2008-2011 based on data from 478 patients. Key findings include:
- Bortezomib-chemotherapy regimens are now preferred for first-line treatment regardless of planned autologous stem cell transplantation (ASCT), which was performed in around 30% of eligible patients.
- Thalidomide- and lenalidomide-based therapies are commonly used in the second-line setting in 31% of patients.
- Cytogenetic testing increased from 23% in 2008 to 53% in 2011 and influences treatment decisions, though age and comorbidities remain major factors.
- Supportive care needs decreased
dual antiplatelet in stroke meta analysisGovind Madhaw
This journal club presentation summarizes a meta-analysis of 18 randomized controlled trials with 15,515 patients comparing dual antiplatelet therapy to mono antiplatelet therapy for secondary stroke prevention in patients with acute ischemic stroke or transient ischemic attack. The meta-analysis found dual antiplatelet therapy significantly reduced the risk of stroke recurrence and composite vascular events compared to monotherapy, without significantly increasing the risk of major bleeding. Sensitivity analyses restricting to double-blind studies showed similar results. The presentation provides details on the search methods, inclusion/exclusion criteria, data extraction, outcomes analyzed, and results of the meta-analysis.
This document summarizes a randomized open-labeled phase IV clinical trial that evaluated the efficacy and safety of adding bromocriptine to metformin therapy in Indian patients with type 2 diabetes mellitus. The trial involved 74 patients randomized into three groups: metformin alone, metformin with 0.8 mg bromocriptine, or metformin with 1.6 mg bromocriptine. HbA1c levels were significantly reduced in all three groups over the course of the trial. Intergroup analysis found no significant differences in HbA1c reduction between the groups. Three patients reported adverse effects in the lower bromocriptine dose group. The study concluded that adding bromocriptine to metformin therapy is more effective in glycemic control compared
This document discusses the role of molecular markers in glioblastoma. It presents a clinical case of a 61-year-old man with glioblastoma who underwent craniotomy and tumor removal. It then poses the clinical question of whether molecular markers in glioblastoma have diagnostic, prognostic, and treatment guidance value. A literature search was conducted in Medline, Scopus, and Cochrane databases using search terms related to molecular markers and glioblastoma. The search identified several papers discussing genetic and tumor markers such as MGMT, EGFR amplification, IDH1, IDH2, and PTEN and their significance for diagnosis, prognosis, and predicting response to treatment. Studies found that markers like methylated MGMT and ID
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Mina Max
This meta-analysis examined 12 randomized controlled trials involving 6,844 patients with advanced non-small cell lung cancer (NSCLC). The analysis compared chemotherapy with or without gefitinib. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The meta-analysis found that gefitinib therapy significantly improved PFS compared to chemotherapy alone, but only modestly improved OS and this difference was not statistically significant. Gefitinib therapy was associated with higher objective response rates. The most common adverse events with gefitinib were rash, diarrhea, and dry skin.
This journal club discussion summarizes a randomized controlled trial that compared the glucose-lowering drug rosiglitazone to metformin and glyburide in patients with recently diagnosed type 2 diabetes. The study was well-designed, experimental in nature, and included over 4,000 patients followed for a median of 4 years. The primary outcome was time to monotherapy failure based on fasting glucose levels. The results showed that rosiglitazone delayed monotherapy failure better than the other drugs and had a lower incidence of progression to higher fasting glucose levels. However, the study also reported some safety concerns with rosiglitazone like increased risk of heart failure. Overall, the discussant found the study to be valid and that the
This study evaluated the drug utilization and rationality of antiepileptic drugs used to treat epilepsy patients at a tertiary care hospital in Dehradun, India. The study found that most epilepsy patients had generalized tonic-clonic seizures. Polytherapy was used more than monotherapy, with 2-drug combinations being most common. First generation antiepileptic drugs like phenytoin were prescribed more than second generation drugs. Phenytoin was the most commonly prescribed antiepileptic drug. The majority of patients receiving polytherapy had a rational drug regimen.
the 1-year cumulative incidence of a composite end point consisting of cardiovascular death, myocardial infarction, ischemic or hemorrhagic stroke, definite stent thrombosis, and major bleeding was 2.4% in the 1-month DAPT group and 3.7% in the 12-month DAPT group, a difference that met the noninferiority margin of a hazard ratio of 0.5, as well as superiority.
This document discusses the proper design of clinical trials in radiology. It reviews key aspects of designing a research study such as defining the research question, reviewing existing literature, determining the appropriate study design, defining the study population and variables, and ensuring precise and accurate measurements. Proper design is important for valid assessment of diagnostic tests. Some key points discussed are that the research question should be important, novel, feasible to answer, ethical, and relevant, and that diagnostic methods are commonly evaluated using randomized blinded trials.
This study evaluated the relationship between Emergency Severity Index (ESI) triage scores, pain medication selection, and timeliness of pain medication administration. The records of 1,966 emergency department patients who received opioid pain medication were analyzed. While there were no significant differences in time to pain medication across ESI levels, patients given higher ESI scores (greater acuity) received stronger opioids more often than those with lower scores. The type of opioid administered differed significantly based on ESI level. However, ESI level was not related to timeliness of pain medication administration.
This meta-analysis reviewed 15 randomized controlled trials involving over 188,000 participants to determine the effect of antioxidant vitamin supplementation on cardiovascular outcomes. The trials assessed supplements containing vitamin E, beta-carotene, and/or vitamin C compared to placebo. The analysis found that antioxidant vitamin supplementation had no significant effect on major cardiovascular events, myocardial infarction, stroke, total death, cardiac death, or other outcomes. There was no evidence that antioxidant vitamin supplements provide cardiovascular benefits.
Multidisciplinary Approach to Prostate Cancer and Changes in Treatment Decisi...CrimsonpublishersCancer
In order to demonstrate the impact of multi-disciplinary care in the community oncology setting, we evaluated treatment decisions following the initiation of a dedicated genitourinary multi-disciplinary clinic (GUMDC).
This study conducted a systematic review and meta-analysis of bariatric surgery outcomes using data from 164 studies published between 2003-2012 including over 161,000 patients. The analysis found that bariatric surgery provides substantial and sustained weight loss and reduction in obesity-related health conditions, though risks of complications, reoperations, and death do exist. Specifically, the 30-day mortality rate was 0.08% and the rate after 30 days was 0.31%. The complication rate was 17% and the reoperation rate was 7%. Greater weight loss was seen with gastric bypass but it had higher complication rates than adjustable gastric banding or sleeve gastrectomy.
This study uses consecutive National Health and Nutrition Examination Surveys (NHANES) data from 2003-2012 to concurrently model obese body size (c.f., normal weight) main effects, moderated by nondiabetic moderate 10-year ASCVD risk (c.f., 30-year and diabetic), on total medical cost outcomes.
• Minors, seniors 76+, outlier diseases, and pregnant women were excluded, resulting in 192,447,424 weighted or 22,510 unweighted participants.
This document discusses evidence-based practice and how it applies to assessing clinical intervention studies. It begins by listing the learning objectives for Lecture c, which include explaining how evidence-based medicine can be applied to intervention studies. The document then discusses how the best evidence for assessing interventions comes from randomized controlled trials (RCTs) or systematic reviews of RCTs. It provides examples of RCTs and outlines key questions one should ask to critically appraise an intervention study, such as whether the results are valid and can be applied to patient care.
Clinical application of statistical analysisUmair hanif
This document provides an overview of key statistical concepts for evaluating medical literature. It describes:
1) The importance of understanding statistics to properly complete and interpret scientific studies, and defines populations, samples, variables, and different types of data.
2) Common study designs and sampling methods used in research like simple random sampling, stratified random sampling, and cluster sampling to obtain representative study samples.
3) The difference between independent and dependent variables, and between discrete and continuous data types. It also outlines the four scales of measurement used in statistics.
The document is intended to provide basic statistical knowledge to help readers better understand and interpret biomedical research studies.
This meta-analysis examined 9 randomized controlled trials involving over 5,000 patients to determine if short-term, intensive statin treatment before coronary procedures reduces the risk of contrast-induced acute kidney injury (CI-AKI). The analysis found that intensive statin treatment significantly lowered the risk of CI-AKI compared to lower dose statins, placebo or no statin, with a relative risk of 0.50. Subgroup analysis showed this risk reduction was significant for patients with acute coronary syndromes, with a relative risk of 0.37, but only a non-significant trend for those without acute coronary syndromes. No evidence of publication bias was detected.
Based on the information provided, the co-chairpersons of the study were:
- Jens D. Lundgren, M.D.
- Abdel G.Babiker, Ph.D.
- Fred Gordin, M.D.
They, along with other members of the INSIGHT START Study Group, assume responsibility for the overall content and integrity of the article.
Weyerhaeuser Co. is a timberland company that owns 13 million acres of land in the United States. It manufactures wood and cellulose fiber products. In 2010, it became a REIT to focus more on its timberland assets. Its largest segments are wood products, cellulose fibers, and timberlands. Analysts have positive opinions on the stock and expect housing starts and timber sales to increase in the coming years.
Before you launch your idea test it and see if there is initial interest. This presentation will help you to test your idea and refine it before you launch. Lets make your idea more successful.
Study of the distribution and determinants of
health-related states or events in specified populations and the application of this study to control health problems.
John M. Last, Dictionary of Epidemiology
The survey analyzed treatment patterns for multiple myeloma in Germany between 2008-2011 based on data from 478 patients. Key findings include:
- Bortezomib-chemotherapy regimens are now preferred for first-line treatment regardless of planned autologous stem cell transplantation (ASCT), which was performed in around 30% of eligible patients.
- Thalidomide- and lenalidomide-based therapies are commonly used in the second-line setting in 31% of patients.
- Cytogenetic testing increased from 23% in 2008 to 53% in 2011 and influences treatment decisions, though age and comorbidities remain major factors.
- Supportive care needs decreased
dual antiplatelet in stroke meta analysisGovind Madhaw
This journal club presentation summarizes a meta-analysis of 18 randomized controlled trials with 15,515 patients comparing dual antiplatelet therapy to mono antiplatelet therapy for secondary stroke prevention in patients with acute ischemic stroke or transient ischemic attack. The meta-analysis found dual antiplatelet therapy significantly reduced the risk of stroke recurrence and composite vascular events compared to monotherapy, without significantly increasing the risk of major bleeding. Sensitivity analyses restricting to double-blind studies showed similar results. The presentation provides details on the search methods, inclusion/exclusion criteria, data extraction, outcomes analyzed, and results of the meta-analysis.
This document summarizes a randomized open-labeled phase IV clinical trial that evaluated the efficacy and safety of adding bromocriptine to metformin therapy in Indian patients with type 2 diabetes mellitus. The trial involved 74 patients randomized into three groups: metformin alone, metformin with 0.8 mg bromocriptine, or metformin with 1.6 mg bromocriptine. HbA1c levels were significantly reduced in all three groups over the course of the trial. Intergroup analysis found no significant differences in HbA1c reduction between the groups. Three patients reported adverse effects in the lower bromocriptine dose group. The study concluded that adding bromocriptine to metformin therapy is more effective in glycemic control compared
This document discusses the role of molecular markers in glioblastoma. It presents a clinical case of a 61-year-old man with glioblastoma who underwent craniotomy and tumor removal. It then poses the clinical question of whether molecular markers in glioblastoma have diagnostic, prognostic, and treatment guidance value. A literature search was conducted in Medline, Scopus, and Cochrane databases using search terms related to molecular markers and glioblastoma. The search identified several papers discussing genetic and tumor markers such as MGMT, EGFR amplification, IDH1, IDH2, and PTEN and their significance for diagnosis, prognosis, and predicting response to treatment. Studies found that markers like methylated MGMT and ID
Chemotherapy+with+or+without+gefitinib+in+patients+with+advanced+non small-ce...Mina Max
This meta-analysis examined 12 randomized controlled trials involving 6,844 patients with advanced non-small cell lung cancer (NSCLC). The analysis compared chemotherapy with or without gefitinib. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The meta-analysis found that gefitinib therapy significantly improved PFS compared to chemotherapy alone, but only modestly improved OS and this difference was not statistically significant. Gefitinib therapy was associated with higher objective response rates. The most common adverse events with gefitinib were rash, diarrhea, and dry skin.
This journal club discussion summarizes a randomized controlled trial that compared the glucose-lowering drug rosiglitazone to metformin and glyburide in patients with recently diagnosed type 2 diabetes. The study was well-designed, experimental in nature, and included over 4,000 patients followed for a median of 4 years. The primary outcome was time to monotherapy failure based on fasting glucose levels. The results showed that rosiglitazone delayed monotherapy failure better than the other drugs and had a lower incidence of progression to higher fasting glucose levels. However, the study also reported some safety concerns with rosiglitazone like increased risk of heart failure. Overall, the discussant found the study to be valid and that the
This study evaluated the drug utilization and rationality of antiepileptic drugs used to treat epilepsy patients at a tertiary care hospital in Dehradun, India. The study found that most epilepsy patients had generalized tonic-clonic seizures. Polytherapy was used more than monotherapy, with 2-drug combinations being most common. First generation antiepileptic drugs like phenytoin were prescribed more than second generation drugs. Phenytoin was the most commonly prescribed antiepileptic drug. The majority of patients receiving polytherapy had a rational drug regimen.
the 1-year cumulative incidence of a composite end point consisting of cardiovascular death, myocardial infarction, ischemic or hemorrhagic stroke, definite stent thrombosis, and major bleeding was 2.4% in the 1-month DAPT group and 3.7% in the 12-month DAPT group, a difference that met the noninferiority margin of a hazard ratio of 0.5, as well as superiority.
This document discusses the proper design of clinical trials in radiology. It reviews key aspects of designing a research study such as defining the research question, reviewing existing literature, determining the appropriate study design, defining the study population and variables, and ensuring precise and accurate measurements. Proper design is important for valid assessment of diagnostic tests. Some key points discussed are that the research question should be important, novel, feasible to answer, ethical, and relevant, and that diagnostic methods are commonly evaluated using randomized blinded trials.
This study evaluated the relationship between Emergency Severity Index (ESI) triage scores, pain medication selection, and timeliness of pain medication administration. The records of 1,966 emergency department patients who received opioid pain medication were analyzed. While there were no significant differences in time to pain medication across ESI levels, patients given higher ESI scores (greater acuity) received stronger opioids more often than those with lower scores. The type of opioid administered differed significantly based on ESI level. However, ESI level was not related to timeliness of pain medication administration.
This meta-analysis reviewed 15 randomized controlled trials involving over 188,000 participants to determine the effect of antioxidant vitamin supplementation on cardiovascular outcomes. The trials assessed supplements containing vitamin E, beta-carotene, and/or vitamin C compared to placebo. The analysis found that antioxidant vitamin supplementation had no significant effect on major cardiovascular events, myocardial infarction, stroke, total death, cardiac death, or other outcomes. There was no evidence that antioxidant vitamin supplements provide cardiovascular benefits.
Multidisciplinary Approach to Prostate Cancer and Changes in Treatment Decisi...CrimsonpublishersCancer
In order to demonstrate the impact of multi-disciplinary care in the community oncology setting, we evaluated treatment decisions following the initiation of a dedicated genitourinary multi-disciplinary clinic (GUMDC).
This study conducted a systematic review and meta-analysis of bariatric surgery outcomes using data from 164 studies published between 2003-2012 including over 161,000 patients. The analysis found that bariatric surgery provides substantial and sustained weight loss and reduction in obesity-related health conditions, though risks of complications, reoperations, and death do exist. Specifically, the 30-day mortality rate was 0.08% and the rate after 30 days was 0.31%. The complication rate was 17% and the reoperation rate was 7%. Greater weight loss was seen with gastric bypass but it had higher complication rates than adjustable gastric banding or sleeve gastrectomy.
This study uses consecutive National Health and Nutrition Examination Surveys (NHANES) data from 2003-2012 to concurrently model obese body size (c.f., normal weight) main effects, moderated by nondiabetic moderate 10-year ASCVD risk (c.f., 30-year and diabetic), on total medical cost outcomes.
• Minors, seniors 76+, outlier diseases, and pregnant women were excluded, resulting in 192,447,424 weighted or 22,510 unweighted participants.
This document discusses evidence-based practice and how it applies to assessing clinical intervention studies. It begins by listing the learning objectives for Lecture c, which include explaining how evidence-based medicine can be applied to intervention studies. The document then discusses how the best evidence for assessing interventions comes from randomized controlled trials (RCTs) or systematic reviews of RCTs. It provides examples of RCTs and outlines key questions one should ask to critically appraise an intervention study, such as whether the results are valid and can be applied to patient care.
Clinical application of statistical analysisUmair hanif
This document provides an overview of key statistical concepts for evaluating medical literature. It describes:
1) The importance of understanding statistics to properly complete and interpret scientific studies, and defines populations, samples, variables, and different types of data.
2) Common study designs and sampling methods used in research like simple random sampling, stratified random sampling, and cluster sampling to obtain representative study samples.
3) The difference between independent and dependent variables, and between discrete and continuous data types. It also outlines the four scales of measurement used in statistics.
The document is intended to provide basic statistical knowledge to help readers better understand and interpret biomedical research studies.
This meta-analysis examined 9 randomized controlled trials involving over 5,000 patients to determine if short-term, intensive statin treatment before coronary procedures reduces the risk of contrast-induced acute kidney injury (CI-AKI). The analysis found that intensive statin treatment significantly lowered the risk of CI-AKI compared to lower dose statins, placebo or no statin, with a relative risk of 0.50. Subgroup analysis showed this risk reduction was significant for patients with acute coronary syndromes, with a relative risk of 0.37, but only a non-significant trend for those without acute coronary syndromes. No evidence of publication bias was detected.
Based on the information provided, the co-chairpersons of the study were:
- Jens D. Lundgren, M.D.
- Abdel G.Babiker, Ph.D.
- Fred Gordin, M.D.
They, along with other members of the INSIGHT START Study Group, assume responsibility for the overall content and integrity of the article.
Weyerhaeuser Co. is a timberland company that owns 13 million acres of land in the United States. It manufactures wood and cellulose fiber products. In 2010, it became a REIT to focus more on its timberland assets. Its largest segments are wood products, cellulose fibers, and timberlands. Analysts have positive opinions on the stock and expect housing starts and timber sales to increase in the coming years.
Before you launch your idea test it and see if there is initial interest. This presentation will help you to test your idea and refine it before you launch. Lets make your idea more successful.
NZA PRESENTACIÓN DE GRABADOS EN VIDRIO Y/O CRISTALNicole Zela Awe
Encuentra el regalo perfecto para toda ocasión
Piezas exclusivas de diseño grabadas a mano, utilizando la técnica de punta y de taladro, según sea el gráfico elegido. Te ayudo a escoger la imagen y/o el tipo de letra más adecuado para la pieza que desees tallar. Si no te convence una imagen en particular te puedo hacer una composición de diseño en base a lo que te gustaría plasmar, dando como resultado piezas exclusivas con diseños personalizados.
Excelentes regalos para cumpleaños, aniversarios , matrimonios, etc.
Keighley Reisenaur spent four amazing months abroad in Sevilla, Spain as a genetics and Spanish major and junior at UW Madison. She lived with a host family in the Triana neighborhood of Sevilla and took field trips to nearby cities like Córdoba, Granada, Portugal, Valencia, Madrid, Barcelona, and Bilbao/San Sebastian. She also visited Rome during her semester abroad and is happy to answer any questions about her experience living in Sevilla.
This document discusses measuring nonenzymatic lysine acetylation in mitochondria. The author hypothesizes that the majority of mitochondrial protein acetylation occurs through nonenzymatic reactions regulated by SIRT3. To test this, the author purified recombinant proteins and used mass spectrometry to quantify acetylation rates of lysine sites when incubated with increasing concentrations of acetyl-CoA or acetyl-P. Preliminary results found one lysine site on PDH and four sites on CKMT were more reactive with acetyl-CoA. Future work includes enzyme activity assays and protein modeling to further understand acetylation effects on protein function and structure.
Why Should I Consider Abolition From Government SchoolsPaul Bass
Lawyer Kevin Novak has a bold assertion. Do you agree? Are you a person of faith? Do you follow the Bible and it's principles? Would you imagine that the Bible says something about where your money goes? This is a presentation from a live webinar by Homeschool Highways host Paul Bass.
The document discusses India's road network and the road infrastructure sector. Some key points:
- India has the second largest road network in the world spanning over 5.23 million kilometres. National highways account for 1.9% of total roads.
- The value of India's roads and bridges infrastructure is expected to reach USD 19.2 billion by FY17 growing at a CAGR of 13.6%.
- The government has increased budget allocations for road development and aims to double the length of national highways to 200,000 kilometres. Private sector participation through PPP models is also growing.
India has the third largest installed power capacity in the world. The government is targeting capacity additions of 88.5 GW under the 12th Five-Year Plan and around 100 GW under the 13th Five-Year Plan through investments of around USD250 billion in the power sector. Renewable energy is also expected to grow robustly, with wind and solar power estimated to contribute 60 GW and 100 GW respectively by 2022. India's power generation has grown significantly over the years at a CAGR of 6.21% between FY10-FY16, with total electricity production reaching 1,107.8 BU in FY16. Thermal power remains the largest source, accounting for over 69% of total installed capacity as
Este documento resume los artículos 98 al 122 de la Ley Orgánica del Trabajo de Venezuela. Estos artículos definen el derecho al salario, su libre estipulación, fijación, disponibilidad e irrenunciabilidad. También cubren temas como el pago de horas extras, feriados y vacaciones, así como el salario base para el cálculo de prestaciones sociales.
Moderator: Christian Villwock (SMI)
Panelists:
Fabian Quosdorf (Wonderlamp)
Ronald Liebermann (Shoutr Labs)
Nico Nonne (Trotzkind)
Michael Geidel (MiriquidiFilm)
Monika Bielskyte (AFE)
Discussion on RA offline streaming with shoutr.Boxx, Things we learned about Story telling in VR, bringing real 3D people to VR, and WebAR vs AppAR
Get to know the Wikitude SDK in its details. Learn what the Wikitude SDK is offering and how it is structured. See the advantages of the Native API vs. the JavaScript API.
Augmented World Expo (AWE) is back for its seventh year in our largest conference and expo featuring technologies giving us superpowers: augmented reality (AR), virtual reality (VR) and wearable tech. Join over 4,000 attendees from all over the world including a mix of CEOs, CTOs, designers, developers, creative agencies, futurists, analysts, investors, and top press in a fantastic opportunity to learn, inspire, partner, and experience first hand the most exciting industry of our times. See more at http://AugmentedWorldExpo.com
Philipp Nagele (CTO, Wikitude) An Insider Deep-Dive into the Wikitude SDK AugmentedWorldExpo
Philipp Nagele (CTO, Wikitude GmbH) gives an Insider Deep-Dive into the Wikitude SDK
An introduction into the many options of the Wikitude SDK with a deeper look into advanced features like Plugins API and how to combine third party libraries with the Wikitude SDK. We will look into the general architecture of the SDK and deep-dive into a few outstanding (and maybe not so well-known) features of the SDK.
Wolfgang Stelzle (RE’FLEKT) Time to make Money with Augmented Reality – Tools...AugmentedWorldExpo
Covering next level AR & VR solutions all the way from prototype to final product. RE’FLEKT CEO Wolfgang Stelzle will explain influences the big five (Apple, Google, Facebook, Microsoft and Samsung) have on making money with AR as well as how enterprises can easily create their own content for an in-house scalable production of AR, VR and 360° Apps. To conclude, he will look at current smart assistant solutions incorporating Augmented and Virtual Reality as a digital assistant for everyday use.
This study compared outcomes for head and neck cancer patients based on age. Younger patients (≤40 years old) had significantly better 5-year survival rates (65%) than middle-aged (41-64 years old, 52%) or older patients (≥65 years old, 38%). Younger patients also developed fewer recurrent tumors or new primary tumors. However, the reasons for the differences in outcomes based on age are unclear. The study aimed to analyze outcomes while controlling for other factors like smoking history, tumor stage, and treatment received to better understand the independent impact of age.
Overall patient satisfaction was significantly higher in homeopathic than in ...home
The results of our systematic review provide limited evidence for the effectiveness of CAM therapy in
relieving symptoms of CFS. However, we are not able to draw firm conclusions concerning CAM therapy for CFS
due to the limited number of RCTs for each therapy, the small sample size of each study and the high risk of bias
in these trials. Further rigorous RCTs that focus on promising CAM therapies are warranted
This systematic review and meta-analysis compares the efficacy of propranolol versus corticosteroids in the treatment of infantile hemangiomas. The review identified 1162 studies, of which 56 met inclusion criteria. For corticosteroids, the meta-analysis included 26 studies and 2629 patients, finding a response rate of 69%. For propranolol, the meta-analysis included 25 studies and 795 patients, finding a response rate of 97%. The differences in response rates between the two treatments were statistically significant. Propranolol appears to be a more effective treatment for infantile hemangiomas with fewer side effects than corticosteroids. However, further randomized controlled trials are still needed.
Translational Genomics towards Personalized medicine - Medhavi Vashisth.pptMedhavi27
This document discusses various approaches to personalized and precision medicine, including stratified medicine, personalized medicine, and precision medicine. It also discusses the role of biomarkers, pharmacogenomics, genetic testing, biobanking, and examples of individualized cancer treatments. Key points include the use of targeted medicines based on disease stage or individual information, and ensuring best outcomes while reducing side effects. The goal of precision medicine is to integrate genomic data to guide health and disease prevention.
Personalized Therapies for OA: Can Biomarkers Get Us There?OARSI
This document discusses the potential for using biomarkers to enable personalized therapies for osteoarthritis (OA). It defines key terms like personalized therapies, biomarkers, phenotypes, and endotypes. The presenter argues that biomarkers could help identify the right treatment for individual OA patients by enabling prognostic and predictive enrichment in clinical trials. However, moving biomarkers from discovery to clinical validation and use involves a long process including assay development, testing biological links and hypotheses, and conducting randomized controlled trials. Several studies are highlighted that have discovered potential new biomarkers and are beginning to test biological links and hypotheses regarding how biomarkers may reflect disease processes and response to treatments.
This document provides guidelines from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs and preferences. Glycemic targets should aim to lower HbA1c levels to <7% but must be tailored based on factors like disease duration, comorbidities, and risks of hypoglycemia. The guidelines emphasize shared decision-making between clinicians and patients and choosing therapies based on each drug's efficacy, safety profile, and costs.
This document provides guidelines from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs and preferences. Glycemic targets should aim to lower HbA1c levels to <7% but must be tailored based on factors like disease duration, comorbidities, and risks of hypoglycemia. The guidelines emphasize shared decision-making between clinicians and patients and choosing therapies based on each drug's efficacy, safety profile, and costs.
This document provides guidelines from the American Diabetes Association and European Association for the Study of Diabetes on the management of hyperglycemia in type 2 diabetes. It recommends a patient-centered approach that considers individual patient needs and preferences. Glycemic targets should aim to lower HbA1c levels to <7% but must be tailored based on factors like disease duration, comorbidities, and risks of hypoglycemia. The guidelines emphasize shared decision-making between clinicians and patients and choosing therapies based on each drug's efficacy, safety profile, costs and patient lifestyle.
The document discusses recent advances in biosimilars and their future prospects. It begins with an abstract about a student's seminar presentation on personalized medicine and pharmacogenomics. The contents section lists topics like what biosimilars are, literature reviews on the use of targeted drugs and clinical trials, the need for and advantages of personalized medicine, and case studies on using genetic testing to target lung cancer treatments. It explores how pharmacogenomics can optimize drug responses based on a patient's genetics and discusses patents and the future of personalized healthcare.
This document summarizes key points from a conference on interrelated autoimmune diseases. It discusses the challenges of determining drug efficacy in clinical trials versus effectiveness in real-world use. For psoriasis treatments, clinical trials only provide a short-term view of efficacy, whereas effectiveness looks at long-term outcomes. A study on psoriasis patients found lower response rates in clinical practice than trials. For IBD treatments, combination therapy with immunosuppressants was more effective than monotherapy in one trial. Clinical trials also show the need for continuous high-dose biologic treatment to reduce antibody development and maintain response.
Lessons learned in polygenic risk research | Grand Rapids, MI 2019Cecile Janssens
1. Fifteen years of polygenic risk research has shown that while polygenic risk scores can statistically significantly associate with complex diseases, the association does not necessarily predict disease risk well enough to be useful in healthcare.
2. To improve prediction, both data and models need to be improved to better reflect the underlying biological complexity. Additionally, predictive performance must be properly evaluated in the intended population and clinical utility determined.
3. Complex diseases are too complex and influenced by many factors to be perfectly predicted by current polygenic risk models. However, prediction does not need to be perfect to be useful, depending on the intended clinical application.
Running Head QUANTITATIVE RESEARCH SUMMARY1QUANTITATIVE RESE.docxtodd581
Running Head: QUANTITATIVE RESEARCH SUMMARY 1
QUANTITATIVE RESEARCH SUMMARY 10
QUANTITATIVE RESEARCH SUMMARY
Student’s Name: Letzy Reyes
Institution: Grand Cayon University
Date: 06/10/2018
Nursing Practice Problem
P-(Problem) – elderly patients aged above 50 years admitted in hospital and having shown blood pressure disease signs. Patients not included in the research were pregnant women.
I-(Intervention) – the patients who are subject in this research will be subjected to therapeutic routine concerning hypertension. The blood pressure of all the patients was tested after administering hypertension medicine to the subjects. The resultant changes were recorded every day to determine the reaction and thus the group will make a conclusion.
C-(Comparison) – institutionalized quality methods will be regulated for hypertension and subjected to the group. The comparison between the groups will be done towards the end of the month in the group.
O-(Outcome) - there will be good relation between the hypertension medication and blood pressure.
T-(Time) – for the next one month the blood pressure will be monitored closely.
The nursing practice portion should be in paragraph form.
PICOT Statement
Elderly patients under hypertension medication together with pharmacological interventions can be maintained in hospitals to improve their blood pressure and with understanding the background and culture of the patients will be of great help in dealing with hypertension. Comment by Doreen Farley: Letzy, I know that this is not the PICOT question that we decided on. What happened to the PICOT?
In patients with hypertension, does the use of meditation along with pharmacological interventions compared to medications alone improve blood pressure? This was the PICOT from out last discussion on 6-1-18
This paper is supposed to be double space only. I am not sure why there is so much space in between concepts.
Introduction
Background of the study
The purpose of the study was to evaluate analyze how patients using hypertension medication along with pharmacological interventions compared to medications alone improve blood pressure. The bottom line of the study was to evaluate how different opinions on hypertension and the treatment of the disease and how such opinions differ from one place to another especially due to the difference in culture or ethnicity of these groups. In addition, the study will be evaluated on what the proposed interventions would do to improve the adherence to these groups. Comment by Doreen Farley: The study evaluated…
The proposed interventions from the research on the two articles will be of importance to the nursing field. There is the need for the nurses to connect, care and convey treatment for various groups of patients in our diverse community. These include taking treatment to patients from different ethnic and racial groups. When it comes to hypertension, nurses have been faced with challenges .
Objective: The prognostic indictors of age-related poor outcomes in patients with acute myeloid leukemia (AML) are still controversial. The aim of this work was to provide comprehensive insights into the effect of different hemocytes and to investigate the association between age and clinical features in adult patients with AML.
Study Design: A retrospective study was performed to determine the role of age in the therapeutic outcomes of AML. A total of 166 newly diagnosed adult patients’ data from January 2015 to November 2019 in Zhongshan Hospital of Xiamen University were collected and analyzed.
Results: Older patients presented a poorer prognosis (p=0.001) with shorter overall survival, which is served as age-related outcomes. Binary logistic regression demonstrated that cytogenetic risk (OR=4.508, 95% CI 2.733–7.435), leukocyte (OR=7.410, 95% CI 1.139–5.910), and bone marrow blast cells (OR=3.261, 95% CI 1.075–5.615) were independent indictors for age-related prognosis. In addition, Kaplan-Meier curve also revealed that the above factors were associated with overall survival (all p values <0.001).
Conclusion: Cytogenetic risk, leukocyte, and bone marrow blast cells are dominant factors which account for the age-related poor outcomes and shorter overall survival in AML.
Keywords: acute myeloid leukemia, adult, cytogenetic risk, hemocyte, leukemia, overall survival
This document summarizes medication use patterns in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. It finds that 85% of ADNI patients took 4 or more daily medications (polypharmacy), and 22% took medications from Beer's list of potentially inappropriate drugs for elderly patients. Memantine treatment was associated with more severe Alzheimer's disease, while cholinesterase inhibitors were prescribed without difference by disease severity. Treatment also differed by gender, age, and education level in both mild cognitive impairment (MCI) and Alzheimer's disease (AD) groups.
This journal club presentation summarizes a study that used real-world clinical data from two UK health trusts to investigate the effectiveness of cholinesterase inhibitors and memantine for dementia. The study found that these medications were associated with a temporary stabilization of cognitive decline for up to 4-6 months. Effectiveness was greater in those with moderate-to-severe impairment and depended on factors like concomitant antipsychotic use and medication switching. Approximately one-third of patients were considered non-responders based on cognitive changes over 6 months before and after treatment.
This document summarizes a study characterizing patients with mild cognitive impairment (MCI) both cross-sectionally and longitudinally. The study found that:
1) Patients with MCI performed similarly to healthy controls on tests of general cognition but scored significantly worse than controls on memory tests, though they performed better than patients with very mild Alzheimer's disease.
2) Over about 4 years of follow-up, 12% of patients with MCI converted to dementia per year, compared to a 1-2% conversion rate in healthy controls.
3) Patients with MCI declined more slowly on cognitive tests than patients with Alzheimer's disease but faster than healthy controls.
This document summarizes a systematic review and meta-analysis of idiopathic sudden sensorineural hearing loss (ISSNHL) in children. The review found that the overall recovery rate for pediatric ISSNHL was 67.91%, similar to adults. A meta-analysis found no significant difference between combined systemic-intratympanic steroid therapy versus solely systemic treatment. The review was limited by the rarity of pediatric ISSNHL and heterogeneity between retrospective case studies. Larger prospective studies are still needed to determine the most effective treatment options for this condition in children.
Perceived benefits and barriers to exercise for recently treated patients wit...Enrique Moreno Gonzalez
Understanding the physical activity experiences of patients with multiple myeloma (MM) is essential to inform the development of evidence-based interventions and to quantify the benefits of physical activity. The aim of this study was to gain an in-depth understanding of the physical activity experiences and perceived benefits and barriers to physical activity for patients with MM.
Hypertension, or high blood pressure, is a growing global health concern that disproportionately affects minority populations like African Americans. The literature review examined 15 research articles on managing hypertension in these high-risk groups. Key findings included: (1) multiple-drug regimens are often needed to control blood pressure; (2) lifestyle modifications can help reduce cardiovascular events; and (3) improving patient education and adherence through culturally-appropriate strategies may enhance health outcomes. Overall, the studies emphasized the importance of early detection, treatment, and prevention to reduce hypertension's harmful effects.
1. 1
Pittala, Keerthana, Elly Ranum, Keighley Reisenauer
Lab 503, 407, 314
5/3/2013
A META-ANALYSIS OF TREATMENTS FOR MYELODYSPLATIC SYNDROME
EVALUATING EFFECTIVENESS OF EPIGENETIC THERAPY, CHEMOTHERAPY,
AND BONE MARROW TRANSPLANT
PRELIMINARY ABSTRACT
Myelodysplastic syndrome (MDS) is a “pre-cancer” of the bone marrow that usually results in
Acute Myelogenous Leukemia (AML). These syndromes involve the degeneration of stem cells
in the bone marrow inducing irregular production of red blood cells. There are several possible
treatments, but the most successful target the genome or the location of cancer. We produced a
meta-analysis of thirty journals, 10 on each type of treatment, and focused on remission rates.
Several databases were used in accumulating data. We addressed the question: of epigenetic
therapy, chemotherapy, and bone marrow transplant, which treatment of MDS is the most
effective in terms of suppression? We concluded that bone marrow transplant was the most
effective treatment (as defined by the highest average score achieved by our index analysis).
INTRODUCTION
“Myelodysplastic syndromes (MDS) include a heterogeneous group of clonal myeloid
stem cell disorders characterized by peripheral cytopenias and dysplasia of bone marrow
progenitor cells” (Candelaria, 2010). Myelodysplastic syndrome is a highly complex disease that
has no known cure. Several treatments are available; among the most commonly used and
researched are epigenetic therapy, chemotherapy, and bone marrow transplant. However, no
2. 2
study has been found that evaluates the effectiveness of each type of these treatments as
compared to each other.
Epigenetic Therapy (Reisenauer)
“Epigenetic mechanisms that can dysregulate gene expression have become increasingly
attractive as potential targets in the therapy of human cancer” (Maslak, 2006). To determine the
best treatment and regimen, a multitude of drugs and treatment regimens have been assayed. An
overall assessment has been achieved that a combination therapy of low dosages and high
intensities will result in the most remissions. “Strategies of combining different drugs aim at
increasing the efficacy of the single agents, therefore improving response rates, prolonging
response duration, and decreasing the toxicities associated with the treatment” (Follo, 2011)
Epigenetic therapy trials define the outcomes of their study in terms of complete remission (CR),
partial remission (PR), and other defined levels of symptom suppression.
Chemotherapy (Ranum)
Lenalidomide has proven to be a promising drug for the treatment of patients with
Myelodysplastic Syndrome. This drug was chosen for this analysis as it is the most widely used
and researched, when compared to other chemotherapy drug regimens. The drug is especially
effective in patients exhibiting a genetic abnormality called 5q syndrome and leads to transfusion
independence in over two thirds of these patients (Ades, 2008). The drug is given in different
amounts and phases depending on the patient. The exact function of Lenalidomide is unknown,
however, as an immunomodulatory agent, it is believed to have several broad biological effects.
The drug can stimulate the immune system by enhancing the response of Cytotoxic T Cells and
Helper T Cells. It is also believed that the drug can slow the growth of blood vessels to prevent
rapid tumor growth (Rami 2011).
3. 3
Bone Marrow/Stem Cell Transplant (Pittala)
Clinical trials show that the effects of Bone Marrow transplants depend on the source,
relatives or an outside source, and the progression of the disease (Anderson, 1993). MDS that has
progressed to serious levels should not respond as actively to Bone Marrow/ Stem Cell
transplants; this progression also depends on the age of patients as the age of contraction and
years with disease influence the treatment type and overall effectiveness (Chunkang, 2007).
The effectiveness of Bone Marrow Transplants, Chemotherapy, and Epigenetic Therapy
is variable. There is no one treatment that has been labeled as the best or most effective method,
as based on our initial literature review; however, by comparing data from additional studies we
can hope to deduce the most effective treatment for patients with MDS. More formally, our
hypothesis is that there is no strong difference between epigenetic therapy, chemotherapy, and
bone marrow transplant in the treatment of MDS. The remainder of this paper will explore this
hypothesis by first describing the methods we used in gathering and analyzing our data. The
results section will highlight our findings; the discussion section will develop the implications of
this data and also explain any shortcomings of the study. The conclusion will recap the findings
and overall process of this study.
METHODS
In completing this meta-analysis, databases were searched using key terms and filtering
techniques. The relevant articles were compared within each treatment type and then cross-
analyzed to determine overall effectiveness. A scale and index (Appendix, Table 2) were
established to analyze success.
4. 4
Epigenetic Therapy
Using PubMed and Web of Knowledge databases to search for information, the key
terms “epigen*”, “MDS”, “Myelodysplastic syndrome”, and “therapy” were searched. Articles
written in English or translated into English were used. Subjects must have a median age over 55
years, no interfering health problems, and be classified with MDS or acute myelogenous
leukemia (AML). The studies must be clinical trials and published after 2000. They must also
report their results in terms of remission or symptom suppression. MDS is most common in older
patients and other interfering health problems could be inadequately accounted in the study, so
these studies were ruled out. Clinical trials were chosen because the focus was on recent work
being applied in a realistic setting to accurately trace the effectiveness of each treatment in “real
time.” No common drug was chosen because the variance between each study was too high.
Studies were excluded if the average age of subjects was below the selected age or if the study
was not conducted on humans. Also, the full article must be available (See Figure 1.3). The type
of trial, subject information, method controls and measurements, and results were recorded in a
table using headers to organize data (see Table 1). Overall, in these studies, CR is defined as
disease stabilization with successful methylation of the targeted gene. PR is considered no
regression or advancement of MDS or AML but without achieving complete stabilization or
remission. Null patients were unable to complete the full treatment regimen due to early death or
alternative complications.
Chemotherapy
Using Medline, Google Scholar, and Web of Knowledge as resources, several articles
were identified relating to the treatment of Myelodysplastic Syndrome using a chemotherapy
regimen of Lenalidomide. The databases were searched using the keywords “Myelodysplastic
Syndrome,” “MDS,” “Lenalidomide,” “chemotherapy,” and “treatment.” Studies that were
5. 5
written in English or translated into English were considered. Because MDS is most commonly
diagnosed in older patients, studies were only considered if they had a median age of at least 60
years old. Studies also needed to have been published in the last 20 years to ensure that the
findings and experimental methods are recent. The studies must involve the use of Lenalidomide
for the treatment of transfusion dependent adults with MDS, and report their results in terms of
treatment independence and/or erythroid response in patients. Studies were excluded if patients
were treated with more than one drug or therapy during their chemotherapy regimen. If the full
article was not available, the study was not considered. The selected articles’ authors’ names,
date of publication, age, sex, and health status of the patients, as well as results of the trials
including erythroid and cytogenic response, were recorded. The citing articles and citations of
related articles were also considered (See Figure 2.3). The information from all the articles was
then organized into an Excel spreadsheet (Table 1).
Bone Marrow/Stem Cell Transplant
Using Pubmed and Google Scholar, articles were found that related to MDS treatment
with Bone Marrow transplants. Data from clinical trials was preferred for the best analysis of a
treatment but retrospective studies provided greater insight into the long-term effects of a
treatment. Retrospective studies took patients from a single location that had undergone Stem
Cell or Bone Marrow transplants and compared their current state to their state during treatment
within a set time span. These studies consisted of patients who had previously received treatment
for MDS but did not benefit from it. Subjects of the studies aged from 3 years to 70+ years, no
age groups were specifically excluded so that the impact of age on treatment could be analyzed.
Articles were compiled using the keywords: “MDS”, “Bone Marrow transplants”, “Acute
Myelogenous Leukemia”, and “suppression”. The articles were then limited to studies done
within the past five years, except for one article which proved to be a basic study done on the
6. 6
subject and was cited by many current studies (Anderson, 1993 ). The data from the articles
collected was then compiled on Excel (Table 1). Data that was recorded included: author, year of
publication, duration of treatment, number of subjects and characteristics, methods and control of
the studies, method of measurement whether statistical or numerical, and the final results. Even
though the fields used for finding articles and studies was very broad this allows for a
consideration of a select few characteristics in patients that are addressed and therefore allow for
a better analysis of the effectiveness of this treatment on certain groups of people. Studies
involving Bone Marrow transplants, including allogeneic bone marrow transplants, and
Hematopoietic cell transplantation were selected. Age of the subjects of the studies was not used
to separate studies (See Figure 3.3). Chance and rate of relapse and overall success of
suppression were used to compare the different treatments.
To compare all these studies between treatments, both an independent scale and an
overarching index analysis were introduced. In the scale, complete remission (CR) consists of
patients who did not relapse within the timeframe of the study and became independent of
regular treatment; partial remission (PR) achieves similar results as CR, but still requires a
degree of treatment continuation and these patients do not fully achieve “success” as defined by
the study; failure to complete the study in full, early death, or placebo treatment is defined as
null. For epigenetic treatment, CR is defined as disease stabilization with successful methylation
of the targeted gene; PR is defined as no regression or advancement of MDS or AML, but
without achieving complete stabilization or remission; null is defined as patients who were
unable to complete the full treatment regimen due to early death or alternative complications. For
chemotherapy, CR is defined as transfusion independence , PR is defined as a reduction in the
number of transfusions needed monthly by at least half , and null is defined as patients who did
7. 7
not complete the treatment regimen or were taking a placebo. For bone marrow transplant, CR is
defined as being disease-free and without relapse within the time frame of the study, PR is
defined as relapse, and null is defined as death directly caused by treatment (not due to relapse)
and includes subjects that could not be used for analysis of partial remissions.
The index was established as a means to compare several variables across each study and
reach numeric conclusions of effectiveness of treatment. Each study was analyzed on length of
trial, number of participants, the percentage of participants showing any positive effects out of
total number of participants, and the percentage of participants showing CR, PR, and Null, again,
out of the total number of participants. A numeric value range was set up for each category
mentioned. A particular study received a number score for each of these variables. The first three
columns give a baseline numeric value to each individual study. From there, studies were given
three separate scores based on the three outcome categories’ (CR, PR, and Null) percentage of
patients that fell within each type of category, respectively. To stratify this data and put more
emphasis on effectiveness, the scale was re-introduced and a value 10 (CR), 5 (PR), or 0 (Null)
was added to each respective group. The total score for each study was, thus, comprised of a
series of three numbers that numerically evaluated the effectiveness of the trial (See Table 2).
The average score for each treatment type was then calculated and used as a comparison between
the studies.
RESULTS
In a cross-study of all the articles between treatment types, no consistent measurement of
treatment success existed. To diminish this, an encompassing definition of symptom suppression
was defined. For our purposes, treatment success was defined as independence from continual
treatment for a length of time and a reduction in cancerous symptoms.
8. 8
Epigenetic Therapy
10 journals were identified as viable epigenetic treatment clinical trial studies of MDS.
Between these ten, 345 patients were identified, all with diagnosed MDS or AML, the secondary
disease to MDS. In these studies, CR is defined as disease stabilization with successful
methylation of the targeted gene. PR is considered no regression or advancement of MDS or
acute myelogenous leukemia (AML), but without achieving complete stabilization or remission.
Null patients were unable to complete the full treatment regimen due to early death or alternative
complications.
Overall, of the 345 patients analyzed, 24% of patients were CR, 47% were PR, and 29%
were null for epigenetic therapy (see Figure 1.1). The average index score for epigenetic
treatment was calculated to be 40.8 (Table 2).
Chemotherapy
10 studies were identified studying the use of Lenalidomide to treat MDS involving a
total of 867 human participants. Transfusion independence is considered to be complete
remission (CR) and a decrease in the number of transfusion needed monthly by at least half is
considered partial remissions(PR). Participants who were taking a placebo or who did not
complete the drug regimen are considered null.
Overall, 336(39%) participants achieved CR, 106(12%) achieved PR and 425(49%) were
considered null(see figure 2.1). The average index score for chemotherapy was 47.9 (see figure
2.2).
9. 9
Bone Marrow/Stem Cell Transplant
The result of allogeneic bone marrow transplants must be observed over the course of
months or years; therefore, most studies were retrospective studies. These studies took patients
who had received bone marrow or stem cell transplants within a certain time frame from a
specific hospital or clinic and followed their progress. The cause of death, rate of relapse, and
disease-free survival are the main topics of interest. The results vary and patients relapsed
depending on the initial severity of MDS. Clinical trials show that the effects of Bone Marrow
transplants depend on the source, relatives or an outside source, and the progression of the
disease (Zimmerman, 2011). MDS that has progressed to serious levels should not respond as
actively to Bone Marrow/ Stem Cell transplants; this progression also depends on the age of
patients as the age of contraction and years with disease influence the treatment type and overall
effectiveness. The levels of red blood cells, neutrophils, and platelets are monitored to measure
the effects of transplants. It was found that allogeneic bone marrow transplants were successful
for individuals with MDS who were under the age of 40; however, the severity of MDS was a
significant determining factor of the effectiveness of treatment (Anderson, 1993). Some younger
patients benefited from treatment but those suffering from MDS, which was a result of
chemotherapy or radiotherapy for cancer, usually resulted in long-term freedom from disease
(Kröger, 2007). This fact was said to be related to the amount of proliferation of MDS before the
time of treatment. Younger patients who received treatment sooner limited the amount of
proliferation making the effects of the treatment more significant. Older patients who had
received treatment were studied, red blood cell count and neutrophil counts were taken, and
various treatments were used to determine the effectiveness of treatment. Many older patients
died because of relapse (Khabori, 2011). Older patients who participated in studies tended to
10. 10
have received previous treatment for MDS including chemotherapy or radiotherapy (Spina,
2012). These patients usually did not respond positively to bone marrow/stem cell transplants
because their condition was worse off compared to younger patients. This showed that bone
marrow transplants and stem cell transplants were helpful in the short term but could not
guarantee the complete prevention of relapse or disease-free survival (Lukenbill, 2013). A
significant portion of patients who underwent treatment relapsed and died about 3-10 years after
treatment due to causes directly related to treatment or because of other adverse causes.
Final Conclusion of Results
For epigenetic therapy 83 (24%) were CR, 162 (47%) PR, and 100 (29%) null. For
chemotherapy, 336(39%) were CR, 106(12%) PR, and 425(49%) null. For bone marrow 572
(34.31%) were CR, 477 (28.61%) PR, and 618 (37.07%) null. Based on these results alone
chemotherapy had the highest percentage of CR patients from score-only analysis. Bone
Marrow/Stem cell transplants had the highest average index score at 56, compared to the other
two treatments, and thusly was deemed the most effective treatment of myelodysplastic
syndrome.
DISCUSSION
In comparing these three treatments, chemotherapy, bone marrow transplant, and
epigenetic treatment, it was concluded that chemotherapy has the highest percentage of patients
who reach CR, but bone marrow transplant has the highest average index score. However, this
comparison is not without error. Each type of treatment focuses on a distinct symptom and
attacks a highly specific cause of MDS. Also, the methods used to study effectiveness and the
metric used to measure progress varied between treatments. For this reason, an overarching scale
and analytical index had to be defined and some of the specific variants of each study were lost.
Also, in order to truly understand which treatment is the most effective, other factors must be
11. 11
taken into account. More research and analysis must be done on the relative safety of the
treatments including what, if any, adverse effects occur during and after treatment. How often
adverse events occur and their severity should also be taken into account. Another important
factor that should be considered is the length of time that a patient remains in remission. MDS
does not have a known cure at this time. As a result, all patients will eventually
relapse. However, the length of time that they remain healthy or treatment independent is also a
factor that changes the effectiveness of a treatment.
Epigenetic Therapy
It is important to note that the indexical analysis of the epigenetic therapy trials is
imperfect. Although this is an efficient and partially reliable means of assessment, this index
does not completely account for all the nuances of each trial. The largest concern is with trials
that do not produce results for a certain scale value, especially CR values. Because the scale is
designed to stratify data, large gaps are used to create distinct separations between the most and
least effective outcomes: CR and null, respectively. If a study does not achieve any CR patients,
a large-scale value is still added to this score and the indexical CR score for that particular study
is deceivingly high. Furthermore, the Follo 2011 Study mentioned “10 healthy, normal
volunteers” that were included in the patient group. However, because these patients’ exact
involvement was not described, only the 20 MDS patients whose treatments were outlined in the
article were included.
Chemotherapy
The comparison of each chemotherapy study to other chemotherapy studies is
unsatisfactory. Though the studies all involve the use of the same drug, Lenalidomide, they vary
in their dosage and treatment schedule. Furthermore, the comparison of chemotherapy to bone
marrow transplant and epigenetic studies is flawed. All the studies use a different metric to
12. 12
measure success. Though the creation of the index helps to compare the studies, it cannot
account for all of the differences between studies.
Bone Marrow/Stem Cell Transplants
Comparing studies that vary in methods, drug concentrations and length of treatment
does not yield perfectly accurate results. There are many discrepancies that must be taken into
account when compiling data and comparing results of studies. The results of some studies
contradicted each other when stating that bone marrow or stem cells were beneficial to the
recipient while other studies stated that treatment was not significant. Statistical measures also
varied from study to study so comparing result was not as accurate.
CONCLUSION
In conclusion, our hypothesis is that there is no significant difference between epigenetic
therapy, chemotherapy, and bone marrow transplant in the treatment of MDS. This paper
explored this hypothesis by first describing the methods we used in gathering and analyzing our
data. The results section highlighted our findings; the discussion section developed the
implications of this data and also any shortcomings of the study. Based on percentages of CR
and the results of our index, Bone Marrow Transplant appears to be the most promising
treatment for MDS among the three treatments studied.
13. 13
REFERENCES
Excel sheet attached in Appendix (Table 1)
Abouyahya et al. 2011, Treatment with Lenalidomide in Myelodysplastic Syndromes with 5q
Deletion; Results From the Patient Named Program (PNP) in the Netherlands.
Ades, et al. 2008, Efficacy and safety of lenalidomide in intermediate-2 or high-risk
myelodysplastic syndromes with 5q deletion: results of a phase 2 study.
Anderson, et al. 1993, Allogeneic bone marrow transplantation for 93 patients with
myelodysplastic syndrome.
Candelaria, Myrna et. al. 2010, Hydralazine and magnesium valproate as epigenetic treatment for
myelodysplastic syndrome. Preliminary results of a phase-II trial.
Chunkang, et al. 2007, Hematopoietic cell transplantation in patients with myelodysplastic
syndrome or acute myeloid leukemia arising from myelodysplastic syndrome: similar
outcomes in patients with de novo disease and disease following prior therapy or
antecedent hematologic disorders.
Claus, Rainer et. al, 2013, Decitabine induces very early in vivo DNA methylation changes in
blasts from patients with acute myeloid leukemia.
Fandy, Tamer E. et, al, 2009, Early epigenetic changes and DNA damage do not predict clinical
response in an overlapping schedule of 5-azacytidine and entinostat in patients with
myeloid malignancies.
Fenaux, et al. 2011, A randomized phase 3 study of lenalidomide versus placebo in RBC
transfusion-dependent patients with Low-/Intermediate-1-risk myelodysplastic
syndromes with del5q.
Follo, M Y, et. al, 2011, Myelodysplasias: Synergistic induction of PI-PLCβ1 signaling by
azacitidine and valproic acid in high-risk myelodysplastic syndromes.
Ho, et al. 2004, Reduced-intensity allogeneic hematopoietic stem cell transplantation for
myelodysplastic syndrome and acute myeloid leukemia with multilineage dysplasia using
fludarabine, busulphan, and alemtuzumab (FBC) conditioning.
Kantarjian, Hagop et. al. 2007, Results of a randomized study of 3 schedules of low-dose
decitabine in higher-risk myelodysplastic syndrome and chronic myelomonocytic
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Khabori, et al, 2011, Impact of intensity of conditioning therapy in patients aged 40-60 years
with AML/myelodysplastic syndrome undergoing allogeneic transplantation.
Klimek, Virginia M. et. al. 2008, Tolerability, Pharmacodynamics, and Pharmacokinetics Studies
of Depsipeptide (Romidepsin) in Patients with Acute Myelogenous Leukemia or
Advanced Myelodysplastic Syndromes.
14. 14
Klisovic, Rebecca B. et. al. 2008, A Phase I Biological Study of MG98, an
Oligodeoxynucleotide Antisense to DNA Methyltransferase 1, in Patients with High-
Risk Myelodysplasia and Acute Myeloid Leukemia.
Kröger, et al. 2007, Autologous stem cell transplantation for therapy-related acute myeloid
leukemia and myelodysplastic syndrome.
Le Bras, et al. 2011, Treatment by Lenalidomide in lower risk myelodysplastic syndrome with
5q deletion—The GFM experience.
List, et al. 2005, Efficacy of Lenalidomide in Myelodysplastic Syndromes.
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Litzow, et al. 2010, Allogeneic transplantation for therapy-related myelodysplastic syndrome and
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Lukenbill, et al. 2013, Defining Incidence, Risk Factors, and Impact on Survival of Central Line-
Associated Blood Stream Infections Following Hematopoietic Cell Transplantation in
Acute Myeloid Leukemia and Myelodysplastic Syndrome.
Majhail, et al. 2012, Reduced-intensity hematopoietic cell transplantation in older patients with
AML/MDS: umbilical cord blood is a feasible option for patients without HLA-matched
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Maslak, P, et. all, 2006, Pilot study of combination transcriptional modulation therapy with
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17. 17
Figure 1.3: This flowchart depicts the online search process for eliminating and selecting various
articles specific to epigenetic treatment.
Search Results (219)
PubMed (123)
Web of Knowledge (96)
Unduplicated Results
n = 219
Duplicates Removed
n = 0
Restriction 1 : English,
Published before 2000
Restriction 2 : Clinical Trials,
Article
Refined Search Results
n = 68
Refined Search Results
n = 210
Excluded Articles:
(n = 9) Restriction 1
(n = 142) Restriction 2
Articles Used:
n = 10
Articles rejected for relevance
after review of Abstract
18. 18
Figure 2.3: This flowchart depicts the online search process for eliminating and selecting various
articles specific to chemotherapy.
Search Results (116)
Medline (41)
Google Scholar (39)
Web of Knowledge (36)
Unduplicated Results
91
Duplicates Removed
25
Restriction 1: Non-primary
sources were excluded
Chemotherapy
Irrelevant Articles
45
Relevant Articles
25
Refined Search Results
70
Refined Search Results
10
2
Articles found through
citations
Excluded Articles:
2 were not available in full
text
Articles Used:
10
Restriction 2 : Report results
in terms of erythroid
response
19. 19
Figure 3.3: This flowchart depicts the online search process for eliminating and selecting various
articles specific to bone marrow transplant.
Search Results (3210)
Pubmed (3201)
Web of Knowledge (9)
Unduplicated Results
n = 3204
Duplicates Removed
n = 6
Restriction 1:
Articles published in past 5
years, Clinical trials, Human
subjects
Bone Marrow/Stem Cell Transplant
Irrelevant Articles
n = 20
Relevant Articles
n = 17
Refined Search Results
n = 37
Refined Search Results
n = 14n = 2
Articles found through
citations
Excluded Articles:
(n = 6) Drug-based treatment
Articles Used:
n = 10
Restriction 2:
Full text available, relevant
bone marrow-based
transplants