Deployment of Preventive Interventions — Time for a Paradigm Shift
New England Journal Of Medicine 2018; 378:1761-1763, DOI: 10.1056/NEJMp1716272
Katherine Pryor, M.D., and Kevin Volpp, M.D., Ph.D.
From the Center for Health Incentives and Behavioral Economics, and the Department of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia.
Successful prevention of diabetes, smoking, etc has been proven many times
The cost of prevention is far less expensive than the cost of treatment
The quality of life is far better if problem is treated than prevented
Examples in article:
- Lifestyle modification reduced T1 Diabetes
- Paying women to not smoke during pregnancy saved lots of health care costs
However
- Insurance companies rarely pay for prevention
The person may no longer be a customer when a health problem is avoided- This is not a problem outside of the US where there is a single payer - have the same customer for life
- Doctors, drug companies, and hospitals get far less income from prevention than from treatment
- The US FDA requires a more expensive proof for prevention vs treatment
Rarely is the proof cost-effective for a single group to fund
See also VitaminDWiki
- Cost Savings with Vitamin D category listing has
158 items along with related searches - VA showed increased vitamin D associated with lower health costs - Lancet May 2012
- UK would save as least 636 million dollars annually by giving 800 IU vitamin D free to all seniors – June 2014
- Curing patients is not a sustainable business model – Goldman Sachs – April 2018
- Preterm birth cost for employers approximately 50,000 dollars – Oct 2017
- And less than $10 of Vitamin D during pregnancy has been proven to cut preterm births in half
- 1 in 4 medical schools have a nutrition course and nutrition counseling is rarely reimbursed, – JAMA Sept 2017
- Reducing fractures with Vitamin D and Calcium saves 3 dollars for 1 dollar invested – Europe Feb 2017
- Do not expect a doctor to recommend a pill which will eliminate his job (vitamin D)
Reason to be optimistic about Vitamin D being different
Vitamin D prevents AND treats MANY diseases (not just one)Proof that Vitamin D Works has the following
ADHD, Alcoholic Liver Cirrhosis, ALS, Alzheimer's, Antibiotic Use in Seniors, Asthma, Autism, Autoimmune Diseases, Back pain, Blood Cell Cancer, Breast Cancer, Cardiovascular, Cholesterol, Chronic Hives, Chronic Kidney Disease, Cluster Headaches, Congestive Heart Failure (Infants), COPD, Crohn's Disease, C-Section and Pregnancy Risks, Cystic Fibrosis, Dengue Fever, Depression, Diabetes, Diabetic Neuropathy, Eczema, Epilepsy, Falls, Fatigue, Fatty Liver (Child), Fibromyalgia, Gestational Diabetes, Gingivitis, Growing Pains, Hay Fever, Heart Attack, Hemodialysis, Hepatitis-C, Hip Fractures, Hypertension, ICU survival, Influenza, Irritable Bowel Syndrome, Ischemic Stroke, Knee Osteoarthritis, Leg Ulcers, Long-COVID, Low Birth Weight, Lupus, Male Infertility, Menstrual Pain, Metabolic Syndrome, Middle Ear Infection (Infants), Mite Allergy, Multiple Sclerosis, Non-Alcoholic Fatty Liver Disease, Osteoarthritis, Parkinson's Disease, Perinatal Depression, Pneumonia (Ventilator-associated), Poor Sleep, PreDiabetes, Preeclampsia, Pre-term Birth, Prostate Cancer, Psoriasis, Quality of Life, Raynaud's Pain, Respiratory Tract Infection, Restless Leg Syndrome, Rheumatoid Arthritis, Rickets, Sarcopenia, Sepsis, Short Neonates, Sickle Cell, Stronger Senior Muscles, Survive ICU, TB, Tonsillitis, Trauma Death, Traumatic Brain Injury, Tuberculosis, Ulcerative Colitis, Urinary Tract Infection, Vaginosis, Vertigo, Warts, Weight Loss__
Reminder: Translate icon in the upper right selects a different language
Click on underlined items for detailsHealth Problem Treat
PreventReduction by Vit D RCT = Randomized Controlled Trial
* = link to additional RCT
CT = Clinical TrialHypertension T P 149 to 142 mm Hg
HT risk reduced 10XRCT* *, 2400 IU. 100,000 IU*
When Vitamin D > 40 ngCardiovascular after attack T 32 % fewer deaths CT 1000 IU Diabetes Type 1 P 85 % 12,000 kids, 2000 IU Diabetes Type 2 T 62 % RCT* CRP reduction, 4000 IU
Injection is far better - RCT *
RCT 50,000 IU/2weeks + probiotics
RCT 5,000 IU daily 6 monthsBack Pain T 95 %
reduced 50%5000/10000 IU
60,000 IU weeklyInfluenza P 90 % RCT *, 2000 IU Falls P 50% RCT, 100,000 IU monthly
RCT with Meals on Wheels 2016Hip Fractures P 30 % RCT * 800 IU Rickets P 98 % Turkey, 400 IU
NOT RCT, given to all childrenRaynaud's Syndrome T 40 % RCT, visual scale, 20000 IU Avg Menstrual pain P 76 % RCT, 7000 IU Avg,
70% reduction 2018
PMS reduced by halfPregnancy risks P 50 % RCT, 4000 IU C-section, unplanned P 50 % RCT, 4000 IU, small study Low birth weight P 60 % RCT * 1000 IU of D2 TB P 60 % RCT, 800 IU Breast Cancer P 60 % RCT, 1100 IU (2007) Rheumatoid Arthritis pain T 40 % RCT, 500 IU, added to prescription Cystic Fibrosis T 75 %
2nd study improvedRCT, pilot 4X fewer deaths 250,000 IU
RCT, pilot 8,200 IUChronic Kidney T 90 to 70 PTH RCT, 3500 IU, Respiratory Tract Infection P 63 % 3 RCT, 4000 IU 1 year 2nd 2000/800 IU
20,000 IU weeklyLupus T
Tzero flares
Pain reducedLoading then 100,000 IU monthly,
RCT too
RCT 4,000 IUSickle Cell T Less pain RCT, up to 100,000 IU/week Leg ulcer healing T 4X faster RCT, 50,0000 IU/week, small study Traumatic Brain Injury T 2X RCT, 20,0000 IU/day with progesterone Parkinson's Disease T Stabilized RCT, 1200 IU/day Multiple Sclerosis P
T68%
95% were CUREDRCT, 7100 IU prevent pre-MS ==> MS
20,000 to 140,000 IU/dayCongestive Heart Failure T 90 % RCT, 1000 IU infants (also: Adults, not RCT) Middle Ear Infection P 30 % RCT, 1000 IU infants Gingivitis T 88 % RCT, 2000 IU Muscle in seniors T 17 % more muscle RCT, 4000 IU Antibiotic use when >70y T 47 % RCT, 60,000 IU monthly Infants taller Benefit 1 cm tall RCT, 50,000 IU weekly,
for 8 weeks while pregnantGestational Diabetes T Reduced 3X RCT, 2 doses of 50,000 IU After Heart Attack T +6% ejection fraction RCT, 800,000 IU one time Prostate Cancer T Fewer +cores RCT, 4000 IU (2012) Asthma P T Reduced symptoms RCT, 60K IU/month;
RCT 50K IU/week
Need good D at 4 weeks into preg.Depression T Reduced RCT 300,000 IU injection
RCT 1500 IU helped Prozac
RCT 50,000 IU weekly, elderlyLow vitamin D
while breastfedP All infants > 20 mg RCT, 5,000 IU Fibromyalgia T Half of many still has Fibro RCT, 30-48 ng
RCT 50K IU/weekHives, Chronic T Reduced 40% RCT, 4000 IU added Cholesterol T Reduced 4 mg RCT, 400 IU + Ca Weight Loss T lost 5 more lbs RCT, 2000 IU +diet +exercise Gestational Diabetes P 40% RCT * , 5,000 IU Chronic Obstructive
Pulmonary DiseaseT 17X improvement CT, 50,000 IU weekly
RCT 100,000 IU monthlyAsthma T 1/2 Asthma attacks RCT >42 mg of vitamin D Quality of Life (QoL) T Nursing Home QoL CT, 4,000 IU in daily bread Death of Critically Ill
PatientsT 20% increase in survivability RCT 540 K IU loading than 90K monthly Restless Leg Syndrome T Score 26 ==> 10 CT, Vitamin D dose size
not stated in abstractHepatitis-C T Aided normal drugs RCT 2.000 IU Crohn's disease T improved when > 30 ng
2nd study fewer relapsesRCT 2,000 IU
10,000 IU RCTPre-term birth P 2.5X decrease, also: fewer
c-section & better ApgarRCT 2,000 IU India Cluster headaches T CH eliminated in 60% 10,000 IU, Mg, Omega-3, etc Autism T 80% improved CT 300 IU/kg/day for 3 months PreDiabetes T ~20% reduced RCT 60,000 IU/month Weight loss:
Overweight and ObeseT 12 lbs in 6 months RCT 100,000 IU/month Sarcopenia = muscle loss T 27% increase RCT 1,000 IU Growing Pains T 60% decrease ~100,000 IU/month -NOT RCT
2nd study, similar resultsOsteoarthritis pain T 60% decrease 50,000 IU/weekly - NOT RCT ALS T helped 2,000 IU - NOT RCT, given to all Vertigo T 3X reduction if raised > 10ng 600,000 IU load, then maint.
NOT RCT, given to allWarts T 80% eliminated injection NOT RCT
60,000 IU/injectionMetabolic Syndrome P reduced 44% when VitD
increased by 30 ngNOT RCT, given to all Hay fever P reduced 48% RCT 1,000 IU for 30 days Preeclampsia P Recurrance cut in half
3 RCT 3.6 X less likely if > 30 ng50,000 IU every 2 weeks
4,000 IU dailyBlood cell cancer
Multiple MyelomaT Survival 90% vs 50% 10,000 IU/week
NOT RCT, given to allIrritable Bowel Syndrome T Reduced 3,000 IU spray RCT Urinary Tract Infection P 50% reduction RCT 20,000 IU weekly Mite Allergy P 5X reduction RCT 2,000 IU preg, 800 IU child Perinatal depression
(depression near birth)T 50% reduction RCT 2,000 IU for just a few weeks Vaginosis T 10X reduction RCT 2,000 IU Eczema T Reduced 2 RCT 1,600 IU Non-Alcoholic
Fatty Liver DiseaseT Reduced RCT 20,000 IU weekly Knee Osteoartiritis T Pain Reduced RCT 60,000 IU monthly after loading dose Tuberculosis T Faster Recovery RCT single 450,000 IU dose Stroke - Ischemic T Faster Recovery RCT single 600,000 IU injection
RCT single 300,000 IU injectionSepsis T Reduce ICU and Hospital
length of stay by 7 days eachRCT 400,000 IU Trauma deaths T 50% fewer deaths Vitamin D & Glutamine
NOT RCT, given to allHemodialysis patients T helped 50,000 IU weekly NOT RCT, given to all Fatty liver - child T 2 X reduction RCT Vitamin D & DHA Fatigue T Reduced 100,000 IU single dose
NOT RCT, given to allSleep Disorders T Nicely treated RCT 50.000 IU bi-weekly Pneumonia
(Ventilator-associated)T RCT Death rate cut in half 300,000 IU injection Infertile males T birth rate doubled RCT 300,000 IU + maint Waist size T Waist size reduced 3 cm 100,000 IU loading + maint for 6 months
for those with Metabolic Syndrome
NOT RCT, given to allAttention Deficient
Hyperactivity DisorderT Reduced
ReducedRCT 3,000 IU for 12 weeks
RCT 50,000 IU weeklyAlcoholic liver cirrhosis T improved survival 1,000 IU of vitamin D NOT RCT Diabetic nephropathy T Reduced HOMA-IR, FRS RCT 50,000 IU weekly Ulcerative Colitis T Reduced 60% RCT 50,000 IU nano daily for a week Obese weight loss T Lost 3X more pounds $10 of Vitamin D added to
calorie restriction & walkingEndometriosis T Nicely treated RCT 50.000 IU bi-weekly Diabetic Wounds T 4X more likely to heal RCT 6,400 daily Alzheimer's T Often reverse Each person gets a different amount of
Vit D, Omega-3, B12, Iron, etcAutoimmune P Decrease 30% RCT Vit D + Omega-3 Smoking T reduce problems RCT 50,000 bi-weekly Tonsillitis T Virtually eliminated RCT 50,000 weekly Epilepsy T Helped 6 ways NOT RCT, given to children & adults Dengue Fever T P Psoriasis T cured 30,000 to 60,000 IU ICU Survival T 2X longer 500,000 IU Long-COVID T 60,000 IU weekly
Most proofs are RCT (Randomized Controlled Trials), where not even the doctor knows who gets it vitamin D- 2 are meta-analyses of multiple RCTs
- Vitamin D was given to ALL infants in the entire country (Rickets) - not an RCT
- In several studies, researchers felt that it was unethical not to give vitamin D to everyone
- In some studies, the dose size varied with the needs of the person (overweight, etc)
- In some studies, the COFACTORS were adjusted to the needs of the patients
- Curing requires the dose size and cofactors to be adjusted to the needs of each patient.
Many Clinical Trials have not found a benefit because of one or more of the following failures:- Fails to use a large enough dose of vitamin D (often < 1,100 IU)
The Even larger dose needed if: 1) obese, 2) poor gut, 3) sick (many diseases consume lots of vitamin D) - Fails to have given vitamin D for a long enough time (a few RCT lasted less than 5 weeks)
- Fails to have given Vitamin D frequently enough. At least every 2 months for D3) - and at least weekly for D2
Note: Infrequent dosing also causes unbalancing of the body's chemistry - Fails to provide a loading dose, or had too short a duration to restore the vitamin D levels
- Fails to use D3 form, instead uses the less effective D2 form
- Fails to have a healthy range of Calcium or other important cofactors (especially for bone-related trials
Also, differences in Magnesium can result in 30% change in response to vitamin D
Magnesium is dependent on water, food, supplements - Fails to notice the pre-existing vitamin D levels - only those who are low will likely show a benefit
- Fails to notice how/when the vitamin D was taken (which can change the response by as much as 2X)
- Fails to report on compliance (in one case 40% of the participants did not take the supplements consistently)
Many Meta-Analyses also do not find a benefit because one or more of the above failures
In addition, many meta-analysis average together ALL of the trials
Imagine a story about a meta-analysis of aspirin (which has never been done)
There would be scores of RCT for aspirin not working with 3 mg doses
There would be a many RCT of aspirin not working with 30 mg doses
There would be a few studies of aspirin WORKING with 300+ mg doses
There would be many studies of small amounts of Willow bark (Vitamin D2 instead of Vitamin D3)
Then there would be a meta-analysis of aspirin and Willow Bark
- That meta-analysis would conclude that aspirin and Willow bark do not work.
See also VitaminDWiki: Random Controlled Trials with vitamin D intervention
- Intervention - Vitamin D
828 Interventions - Note: It sorts the interventions by health problem as well as by date
29866 Vitamin D clinical trials as of Jan 2025: Nutrition Disorders 621, Vitamin D Deficiency 619, Malnutrition 601, Avitaminosis 586, Deficiency Diseases 583, Metabolic Diseases 489, Musculoskeletal Diseases 362, Bone Diseases 317. Bone Diseases, Metabolic 282, Endocrine System Diseases 241. Osteoporosis 209, Immune System Diseases 190, Kidney Diseases 168, Communicable Diseases 164. Infection etc.- Systematic Reviews or Meta-Analysis of Vitamin D
668 items - 137 health problems associated with low vitamin D – meta-meta-analysis April 2014
- Intervention - 2-30 days
273 items More intervention trials for Vitamin D than for the TOTAL of Vitamins A + C + K combined
Vitamin D = 2199, Others = 1803 Vitamin A 702 + Vitamin C 768 + Vitamin K 333 as of Aug 2020
See also VitaminDWiki
- Overview: Vitamin D also TREATS
- Is it ethical to not give vitamin D in osteoporosis trials– NEJM Sept 2010
- Some Vitamin D RCT are not being created because the researchers do not want to deprive the benefits to half of the patients
- Some Vitamin D RCT cannot be started because too many candidates are already taking vitamin D
- Reasons for Vitamin D deficiency
- List of all categories of Vitamin D Information and number of items in each
- List of all Overviews of Vitamin D
69 items along with related searches
CLICK ON chart for more information and translationVitamin D is especially needed during pregnancy
Most were taking 2,000 to 7,000 IU daily for >50% of pregnancy
Click on hyperlinks for detailsProblemVit. D
ReducesEvidence 0. Chance of not conceiving 3.4 times Observe 1. Miscarriage 2.5 times Observe 2. Pre-eclampsia 3.6 times RCT 3. Gestational Diabetes 3 times RCT 4. Good 2nd trimester sleep quality 3.5 times Observe 5. Premature birth 2 times RCT 6. C-section - unplanned 1.6 times Observe Stillbirth - OMEGA-3 4 times RCT - Omega-3 7. Depression AFTER pregnancy 1.4 times RCT 8. Small for Gestational Age 1.6 times meta-analysis 9. Infant height, weight, head size
within normal limitsRCT 10. Childhood Wheezing 1.3 times RCT 11. Additional child is Autistic 4 times Intervention 12.Young adult Multiple Sclerosis 1.9 times Observe 13. Preeclampsia in young adult 3.5 times RCT 14. Good motor skills @ age 3 1.4 times Observe 15. Childhood Mite allergy 5 times RCT 16. Childhood Respiratory Tract visits 2.5 times RCT RCT = Randomized Controlled Trial
Also, The Vitamin D Receptor limits the amount of Vitamin D in the blood actually gets to the tissue
The risk of 48+ diseases at least double with poor Vitamin D Receptor
Short URL = is.gd/dproof
__
In 2002, Knowler et al. reported results of a landmark study — a large, randomized, controlled trial comparing a behavioral intervention with medical therapy in the prevention of diabetes.1 Over a mean follow-up period of 2.8 years, the lifestyle-modification program, known as the Diabetes Prevention Program (DPP), reduced the incidence of diabetes by 58% as compared with placebo among people with elevated fasting and post-load plasma glucose concentrations. Metformin reduced the incidence of diabetes by 31% as compared with placebo.Despite these findings, insurers have been slow to provide coverage for DPP-like interventions. In 2016, the Centers for Medicare and Medicaid Services piloted the program and determined that it improved the quality of patient care and reduced net Medicare spending, prompting a goal of expanding the DPP nationwide by 2018. Although coverage of metformin has been ubiquitous since it was introduced in the United States in 1995, many private insurers started covering the DPP only recently.
Financial incentives for tobacco cessation during pregnancy provide another example of an effective behavioral intervention that hasn’t been translated into practice. Smoking during pregnancy is a leading cause of maternal and neonatal morbidity and mortality, particularly among socially disadvantaged women and their children, and has long been a public health target. In the United States, such smoking rates have decreased only marginally in recent decades. A Cochrane review concluded that financial incentives are the most effective intervention in this population and can lead to quit rates up to four times higher than those achieved with other interventions. But such incentives haven’t been implemented in routine care of pregnant women.
Why are highly effective preventive interventions adopted slowly, if at all? The first issue is that, historically, far more resources have been devoted to treating disease than to preventing it; in 2015, only 3% of health care dollars were spent on preventive services. However, ongoing shifts in health financing are creating incentives for providers to pay more attention to modifiable risks such as antenatal smoking. Hospitals participating in accountable care organizations, for example, save thousands of dollars for each neonatal intensive care unit stay they prevent.
Second, treatments determined by the Food and Drug Administration (FDA) to be safe and effective are usually covered by insurers regardless of their cost, but preventive services have been held to a higher standard: they are often assessed on the basis of whether they generate a positive return on investment and save money in the short term. This disparity leads to overprovision of treatments and underprovision of preventive services, a trend that is exacerbated by high turnover in many health insurance markets. Because insurance contracts tend to be only 1 year long, insurers don’t want to spend money to prevent disease in members who may be covered by a different insurer in the near future.
Even Medicare — which typically covers beneficiaries for life — holds preventive services to a higher standard, applying cost-effectiveness analyses when making coverage decisions about preventive services but not treatments. This double standard has resulted in coverage of cost-ineffective therapies with prices of up to hundreds of thousands of dollars per quality-adjusted life-year, including treatments of questionable benefit (such as Avastin bevacizumab for metastatic breast cancer after the FDA withdrew support for this use).2 A recent study showed that reallocating current Medicare expenditures toward “dominant” (cost-saving and health-increasing) interventions would result in efficiency gains and improvement in the aggregate health of Medicare beneficiaries at no additional cost. 3
Third, behavioral interventions often represent unfamiliar territory for providers. Writing a prescription is generally easy and routine, and medications are heavily marketed and seen as being easier to broadly disseminate with predictable efficacy. But this assumption doesn’t always hold true. The diabetes-prevention trial, for example, found a less heterogeneous effect in the behavioral-intervention group than the metformin group: the DPP was associated with a substantial reduction in the incidence of diabetes regardless of patients’ baseline risk, but only the highest-risk patients in the metformin group saw a similar benefit.4
Fourth, many providers seem largely unaware of the high rates of medication nonadherence among their patients and don’t have effective tools for improving adherence. Prescribing a medication is simple for a provider, but taking a medication does not appear to be simple for many patients. Outside of clinical trials, adherence to medications is often low. In the year after a heart attack, for example, only 40 to 45% of patients take their medications as prescribed.
Finally, concerns about scalability are often a barrier in the deployment of proven behavioral interventions. Consider financial incentives for antenatal smoking cessation: such a program would require an intensive schedule of in-person visits for biochemical assessment of abstinence. Although such assessments could be built into the standard prenatal care schedule in which urine collection during office visits is common, the program would still require a shift in what providers do during visits. Assessing smoking status and counseling against ongoing tobacco use are already part of the routines of antenatal care providers, but overseeing a reward system tied to smoking cessation would be new. There is no readily available infrastructure for clinics to manage such a program, and developing one might require a third party. Health plans could be the third party that assesses cotinine test results and administers rewards, but this would need to be done in a way that minimizes delays and administrative complexity.
These barriers signal a need to rethink and optimize the infrastructure and platforms on which health services are currently delivered. For example, leveraging Web-based technologies or wireless devices would address many scalability concerns and help facilitate adoption of certain behavioral interventions. Consider the DPP-like behavioral intervention: it is labor- and time-intensive for both staff and participants, with requirements including supervised physical-activity sessions, individualized coaching, and case managers. There are geographic limitations in availability, and only a small fraction of people with prediabetes enroll. However, online versions of DPP-like interventions now exist and feature greater schedule flexibility, a personal coach, and online peer-support groups, eliminating the need for in-person assessments. Online programs result in weight loss similar to that seen in the standard DPP.5 Web-based platforms have been used successfully in contingency management for both chronic disease and substance abuse. In these programs, biochemical markers such as carbon monoxide and blood glucose or vital signs such as blood pressure can be assessed by means of virtual observation of patients using monitoring equipment in their homes. Such platforms facilitate important innovations in supporting management of a growing range of diseases and care for hard-to-reach populations.For health care’s transformation from a volume- to a value-based framework to be successful, we think that putting coverage of preventive services and treatments on more even footing will deliver great value. Historically, preventive services have been adopted only if they have been proven to save money, whereas treatments have been evaluated on the basis of their benefits and risks, without consideration of costs. The slow movement toward coverage and implementation of behavioral interventions may accelerate substantially as population-based financing becomes the norm. Payment reform has the potential to bring about a paradigm shift whereby all services are evaluated using the same standard: Do they improve health at a reasonable price? Such a shift could increase insurers’ willingness to cover high-value preventive services and providers’ interest in designing ways to facilitate the uptake and deployment of those services on a broader scale — enabling us to achieve better health at lower cost.
References
- 1. Qaseem A, Snow V, Gosfield A, et al. Pay for performance through the lens of medical professionalism. Ann Intern Med 2010;152: 366-9.
- 2. Berwick DM. Era 3 for medicine and health care. JAMA 2016;315:1329-30.
- 3. Casalino LP, Gans D, Weber R, et al. US physician practices spend more than $15.4 billion annually to report quality measures. Health Aff (Millwood) 2016;35:401-6.
https://doi.org/10.1377/hlthaff.2015.1258 available at sci-hub
“A study of twenty-three health insurers found that 546 provider quality measures were used, few of which matched across insurers 10 or with the 1,700 measures used by federal agencies”
“State and regional agencies currently use 1,367 measures of provider quality”
“The current system is far from being efficient and contributes to negative physician attitudes toward quality measures.” - 4. Higashi T, Shekelle PG, Adams JL, et al. Quality of care is associated with survival in vulnerable older patients. Ann Intern Med 2005;143:274-81.
- 5. Hemingway H, Crook AM, Feder G, et al. Underuse of coronary revascularization procedures in patients considered appropriate
candidates for revascularization. N Engl J Med 2001;344:645-54.
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