Key Articles Flashcards
Which of the following statements about the Ornish Lifestyle Heart Trial are correct?
A. It used a pre versus post design with each subject serving as their own control.
B. It compared a low-fat diet to a low-carb diet in the secondary prevention of coronary artery disease.
C. The treatment group had a relative difference in progression of -35.6% at five years compared to all controls, and a difference of -54.6% compared to controls not taking lipid-lowering medications.
D. There was no association between adherence and change in stenoses or risk factors.
E. None of the above.
C.
The treatment group had a relative difference in progression of -35.6% at five years compared to all controls, and a difference of -54.6% compared to controls not taking lipid-lowering medications.
The study used a randomized parallel design, not pre versus post.
It compared a low-fat diet to usual care, which typically recommends the American Heart Association (AHA) Step 2 diet (not a low-carb diet) for patients with diagnosed CAD.
There was a strong dose-response relationship between self-reported adherence and angiographic changes.
The treatment group had a 7.9% reduction in stenoses at five years, while all controls had a progression of 27.7%, for a net difference of -35.6%.
Those controls who were not taking lipid-lowering medications had a progression of 46.7%, for a net difference of -54.6%.
*Intensive lifestyle changes for reversal of coronary heart disease. Ornish et al. JAMA. 1998:280(23):2001-7.
All of the following statements about the Ornish Lifestyle Heart Trial are false EXCEPT:
A. It used a randomized, double-blind, parallel cohort design.
B. It compared a low-fat diet and smoking cessation to usual care.
C. It compared intensive lifestyle interventions to non-intensive lifestyle interventions.
D. In spite of its small sample size, the trial found both statistically significant and clinically significant differences between optimal usual care and intensive lifestyle treatment.
E. Both C and D.
E. Both C and D.
The study was randomized parallel but not double-blind.
It compared a multifactorial lifestyle intervention (a low-fat vegetarian diet, aerobic exercise, stress management, smoking cessation and group psychosocial support) to optimized usual care, not merely low-fat diet and smoking cessation, as answer B stated.
The study did compare intensive lifestyle changes to non-intensive lifestyle changes, because the control group was instructed to follow their doctor’s lifestyle recommendations and received written information about the AHA Step 2 diet.
The study had a small number of subjects, but the differences were highly significant, both clinically and statistically, as there were far fewer cardiac events among the experimental group, and most differences had p-values <0.05.
*Intensive lifestyle changes for reversal of coronary heart disease. Ornish et al. JAMA. 1998:280(23):2001-7.
Which of the following statement(s) about the Knowler NDPP study are correct?
A. It was a randomized clinical trial comparing the effect of intensive lifestyle modification or metformin with a control group receiving a placebo.
B. The primary outcome measure of this trial was weight reduction.
C. The trial was stopped prematurely after two years of follow-up.
D. Since the trial was not a multi-center trial, the generalizability of the findings is reduced.
E. None of the above are correct.
A.
It was a randomized clinical trial comparing the effect of intensive lifestyle modification or metformin with a control group receiving a placebo.
The primary aim of the study was a reduction of diabetes and not a reduction of weight
The change in weight was a secondary outcome.
The trial was stopped prematurely after 2.8 years, not two years.
It was a multicenter trial, so the results can be generalized to a wide population of similar subjects.
*Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. Knowler et al. N Engl J Med. 2002 Feb 7;346(6):393-403.
Which of the following best summarizes the findings of the Knowler NDPP study?
A. As compared to the control group, subjects in the intensive lifestyle modification group demonstrated no change in their risk of diabetes or weight.
B. As compared to the control group, subjects in the intensive lifestyle modification group demonstrated decreased risk of diabetes but had no change in their weight.
C. As compared to the control group, subjects in the intensive lifestyle modification group demonstrated no change in their risk of diabetes but they decreased their weight.
D. As compared to the control group, subjects in the intensive lifestyle modification group demonstrated a reduction in both their risk of diabetes and in their weight.
E. The intensive lifestyle modification reversed type 2 diabetes.
D.
As compared to the control group, subjects in the intensive lifestyle modification group demonstrated a reduction in both their risk of diabetes and in their weight.
The lifestyle modification group did not reverse type 2 diabetes because the subjects did not have type 2 diabetes, they only had impaired glucose tolerance, or prediabetes. (This was a prevention trial, not a disease reversal trial).
*Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. Knowler et al. N Engl J Med. 2002 Feb 7;346(6):393-403.
The aim of the portfolio diet study by Jenkins et al was to show:
A. A low-fat diet was better than statins for treating hypercholesterolemia.
B. A low-fat diet was equally efficacious as statins in lowering serum lipid levels.
C. The effectiveness of reducing serum cholesterol levels using a diet containing a portfolio of various dietary factors that reduce cholesterol as compared to statins.
D. The effectiveness of reducing serum cholesterol levels using a diet very low in saturated fats as compared to statins.
E. The comparison of a low-fat diet to a low-carbohydrate diet and to usual care for lowering serum cholesterol.
C.
The effectiveness of reducing serum cholesterol levels using a diet containing a portfolio of various dietary factors that reduce cholesterol as compared to statins.
The purpose of the study by Jenkins et al was “to determine whether a diet containing the recommended food components (low saturated fat, with plant sterols and viscous fibers, and soy protein and nuts) leads to cholesterol reduction comparable with that of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins).”
*Effects of a dietary portfolio of cholesterol-lowering foods versus lovastatin on serum lipids and C-reactive protein. Jenkins et al. JAMA. 2003 Jul 23;290(4):502-10.
In the portfolio diet study by Jenkins et al, reduction in which of the following could be considered as an adverse event:
A. LDL
B. HDL
C. Total cholesterol
D. LDL-C: HDL-C ratio
E. Total cholesterol: HDL-C ratio
B. HDL
Improvement in metabolic profile is typically associated with increased HDL and a reduction in other cholesterol subtypes and ratios.
Although a transient reduction in HDL may be seen with dietary modifications, sustained reduction in HDL could be considered an adverse event.
*Effects of a dietary portfolio of cholesterol-lowering foods versus lovastatin on serum lipids and C-reactive protein. Jenkins et al. JAMA. 2003 Jul 23;290(4):502-10.
Based on results in the figure and the table in Hambrect CAD study, which of the following is the most appropriate conclusion?
A. As compared to the PCI group, resting heart rate was statistically significantly higher in the exercise training group at the end of the study.
B. As compared to the PCI group, maximal heart rate was statistically significantly lower in the exercise training group at the end of the study.
C. As compared to the PCI group, physical work capacity was statistically significantly higher in the exercise training group at the end of the study.
D. As compared to the PCI group, VO2 max was statistically significantly lower in the exercise training group at the end of the study.
E. As compared to the PCI group, the exercise training group had ~25% greater risk of cardiac events (70% versus 88%).
C.
As compared to the PCI group, physical work capacity was statistically significantly higher in the exercise training group at the end of the study.
In the exercise training group, physical work capacity increased from 133 at baseline to 159 at the end of the study. This change was statistically significant as compared to almost no change observed in the PCI group.
The resting heart rate was lower in the exercise-training group, and the maximal heart rate and VO2 max were higher in the exercise-training group at the end of the study as compared to the PCI group.
The exercise group was 88% event free after 12 months, compared to only 70% of the PCI group, resulting in a 26% lower risk in the exercise group than the PCI group
*Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease: a randomized trial. Hambrecht et al. Circulation. 2004 Mar 23;109(11):1371-8.
Which of the following statements is FALSE regarding the Hambrecht CAD study?
A. Exercise training was more cost effective as compared to PCI with respect to changing the Canadian Cardiovascular Risk Class.
B. Exercise training was less cost effective as compared to PCI with respect to changing the Canadian Cardiovascular Risk Class.
C. Exercise training was more cost effective as compared to PCI with respect to changing the Canadian Cardiovascular Risk Class and improving exercise capacity.
D. Exercise training was less cost effective as compared to PCI with respect to changing the Canadian Cardiovascular Risk Class and improving exercise capacity.
E. B and D are both false.
E. B and D are both false.
Exercise training cost $3,429 to change by one class of the Canadian Cardiovascular Society as compared to PCI which cost $6,956.
Exercise training was superior to PCI in improved exercise capacity at lower costs largely due to lower repeat hospitalizations and revascularizations.
Therefore, exercise training was more cost effective as compared to PCI for both Canadian Risk Class and exercise capacity.
*Percutaneous coronary angioplasty compared with exercise training in patients with stable coronary artery disease: a randomized trial. Hambrecht et al. Circulation. 2004 Mar 23;109(11):1371-8.
The most accurate conclusion from Ornish Diet, Weight Loss and HD study would be:
A. The type of diet was associated with weight loss but not with adherence.
B. Adherence levels were associated with weight loss but not with the type of diet.
C. Both adherence and the type of diet were important predictors of weight loss.
D. Neither diet nor adherence were predictors of weight loss.
E. Adherence largely determined treatment effects and weight loss.
E.
Adherence largely determined treatment effects and weight loss.
The graph demonstrates that as adherence scores increase, weight loss increases regardless of the dietary program the participants are following. This indicates that a level of adherence is more important that the type of dietary program the participants are following.
*Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. Dansinger et al. JAMA. 2005 Jan 5;293(1):43-53.
The amount of variability in the weight loss achieved by the participants in the Ornish Diet, Weight Loss and HD study demonstrates that one of the major take home messages from this trial is:
A. Dietary changes are not useful for weight loss.
B. The effects of dietary changes drops the longer a subject is on the diet.
C. It’s important to match the right individual to the right lifestyle modification program.
D. The role of exercise is important for weight reduction and is not taken into account in this trial.
E. The intensity of the intervention may be more important than the specific diet for weight loss.
E.
The intensity of the intervention may be more important than the specific diet for weight loss.
Weight loss was more strongly associated with adherence level than with the specific diet in this study. The intensity of the treatment is directly related to adherence, thus intensity may be more important than diet type for weight loss.
*Comparison of the Atkins, Ornish, Weight Watchers, and Zone diets for weight loss and heart disease risk reduction: a randomized trial. Dansinger et al. JAMA. 2005 Jan 5;293(1):43-53.
The GEMINAL study is a pivotal study demonstrating the effect of lifestyle modification at the genetic level. Which of the following is the most prominent limitation of this study?
A. Short follow-up time.
B. Small sample size.
C. Absence of a comparison group.
D. Number of genes studied was too large, reducing the possibility for multiple comparisons.
E. None of the above are serious limitations.
C. Absence of a comparison group.
The most significant limitation of the GEMINAL study is the absence of a comparison group. Absence of a control group prevents us from definitively saying that the gene expression changes are due to the comprehensive lifestyle modification and not due to normal changes in gene expression.
The GEMINAL study presents high quality preliminary data that can be used to design future clinical trials that have appropriate control groups.
Although multiple comparisons are always a concern when a large number of data points are being analyzed, this was corrected for using a Bonferroni correction.
Small sample size and short follow-up are not major limitations, especially given the fact that the results are statistically significant as this indicates to us that the effect size is large enough to overcome the negatives associated with small sample size and short follow-up.
*Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Ornish et al. Proc Natl Acad Sci USA. 2008 Jun 17;105(24):8369-74.
Among the biopsies used in the GEMINAL study, only 30% contained tumor tissue, so the results demonstrating changes in gene expression profiles are largely based on normal tissue. Which of the following is an appropriate statement?
A. Since the results are based on mainly normal tissue, these results indicate that the impact of lifestyle modification is not restricted to prostate cancer.
B. Since the results are based on mainly normal tissue, these results are questionable.
C. Since the results are based on mainly normal tissue, these results indicate that the impact of lifestyle modification does not impact prostate cancer.
D. Since the results are based on mainly normal tissue, these results apply more to men without prostate cancer than with it.
E. Both A and B are true.
A.
Since the results are based on mainly normal tissue, these results indicate that the impact of lifestyle modification is not restricted to prostate cancer.
Since only 30% biopsies had tumor tissue, these results are mainly based on normal tissue from men with prostate cancer. This indicates to us that lifestyle modification can affect both cancer and normal tissue, and thus the benefits of lifestyle modification has a wide applicability and is not restricted to genes associated with prostate cancer.
That the findings are based largely on normal tissue does not invalidate the findings, therefore response B is incorrect.
Also, although the results are largely based on normal tissue in men with prostate cancer, that doesn’t mean these results indicate that lifestyle modification does not apply to prostate cancer, so response C is incorrect.
Response E is incorrect since response B is incorrect.
*Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Ornish et al. Proc Natl Acad Sci USA. 2008 Jun 17;105(24):8369-74.
In Ornish telomere and prostate cancer study, Telomere shortness is an indicator of:
A. Increased morbidity and shorter lifespan.
B. Increased morbidity and longer lifespan.
C. Decreased morbidity and longer lifespan.
D. Decreased morbidity and shorter lifespan.
E. Abnormal aging.
A. Increased morbidity and shorter lifespan.
Longer telomere length is associated with increased longevity and reduced morbidity. Therefore, shorter telomere length would be associated with increased morbidity and shorter lifespan. Decreased telomere length occurs with the typical aging process.
*Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Ornish et al. Lancet Oncol 2013; 14: 1112–20
Based on the results of Ornish telomere and prostate cancer study, the next step in the process would be:
A. To advise patients to adopt a comprehensive lifestyle modification approach to increase the length of their telomeres.
B. To write a case report detailing the changes in individual patient’s lifestyle modification program and its effects on their telomere lengths.
C. To conduct a randomized controlled study with a larger sample size.
D. To conduct a case-control study.
E. To conduct a repeat pilot study in women.
C. To conduct a randomized controlled study with a larger sample size.
Lifestyle modification is the best approach to reducing morbidity and mortality and to improving quality of life for most disease types. But based on the results of this study, lifestyle modification’s effectiveness in increasing telomere length is yet to be established. The study results look promising. However, they aren’t adequate to change current clinical practice with respect to telomere length. Therefore, the next step would be to conduct a randomized controlled study in a larger population. If the results of the randomized study demonstrate the same effect on telomere length, that would be grounds to change clinical practice. Case series and case-control studies are not the appropriate responses, as these should already have been conducted before a comparative longitudinal study as described in the current paper. It’s unnecessary to repeat the pilot until further evidence is available in males.
*Effect of comprehensive lifestyle changes on telomerase activity and telomere length in men with biopsy-proven low-risk prostate cancer: 5-year follow-up of a descriptive pilot study. Ornish et al. Lancet Oncol 2013; 14: 1112–20
Which of the following statements about the Lim Counterpoint study are FALSE:
A. This study used a case-control design with matched controls.
B. The intervention included a very low calorie diet of 600 kcal per day.
C. The primary outcomes were beta cell function and insulin sensitivity.
D. Most of the improvement occurred in the final four weeks of the study.
E. Fatty liver and fatty pancreas both improved with the very low-calorie diet.
D. Most of the improvement occurred in the final four weeks of the study.
The study used a case-control design with non-diabetic controls (matched for age, gender and weight).
The intervention consisted of a total energy intake of ~600 kcal per day. This included 510 kcal per day liquid diet formula (comprised of 46.4% carbohydrate, 32.5% protein and 20.1% fat; vitamins, minerals and trace elements) supplemented with three portions of non-starchy vegetables.
The hypothesis tested was that beta cell failure and insulin sensitivity can be reversed with dietary restriction.
Most of the improvement occurred in the first week (not the last four weeks). Dietary restriction significantly reduced both fatty liver and fatty pancreas.
*Reversal of type 2 diabetes: normalization of beta cell function in association with decreased pancreas and liver triacylglycerol. Lim et al. Diabetologia. 2011 Oct;54(10):2506-14.
