Exploring the subtleties of inverse probability weighting and marginal structural models

Since being introduced to epidemiology in 2000, marginal structural models have become a commonly used method for causal inference in a wide range of epidemiologic settings. In this brief report, we aim to explore three subtleties of marginal structural models. First, we distinguish marginal structural models from the inverse probability weighting estimator, and we emphasize that marginal structural models are not only for longitudinal exposures. Second, we explore the meaning of the word ‘marginal’ in ‘marginal structural model.’ Lastly, we show that the specification of a marginal structural model can have important implications for the interpretation of its parameters. Each of these concepts have important implications for the use and understanding of marginal structural models, and thus providing detailed explanations of them may lead to better practices for the field of epidemiology

Conflicts of interest: The authors declare no conflicts of interest

Financial support: This work was supported by National Institutes of Health grants R01AI100654 (SRC) and DP2HD084070 (DW).

Correspondence to: Alexander Breskin, Department of Epidemiology, University of North Carolina at Chapel Hill, CB 7435 McGavran-Greenberg Hall, Chapel Hill, NC 27599, abreskin@unc.edu, (917) 593 9004

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Exploring the subtleties of inverse probability weighting and marginal structural models

The Effects of Long-Term Storage on Commonly Measured Serum Analyte Levels


Cohort studies typically bank biospecimens for many years prior to assay and investigators do not know whether levels of analytes have degraded.


We collected control samples from 22 non-study participants using the same enrollment criteria and specimen collection, processing, and storage protocols as The Sister Study. Serum samples were assayed for 21 analytes at collection and 6 years later. For each sample, the difference between the result at baseline and at 6 years was calculated for each analyte.


Some of the analytes experienced a marked decrease in concentration after six years of frozen storage in liquid nitrogen vapor, compared to their baseline value. The confidence interval for the mean paired difference excluded 0 for 8 of the 21 analytes tested (aspartate transaminase, total cholesterol, estradiol, glucose, HDL cholesterol, luteinizing hormone, protein, and triglycerides). Two analytes, lactate dehydrogenase and sex hormone binding globulin, increased substantially in concentration over time (confidence interval excluded 0). For compounds substantially affected by storage time, the internal laboratory control variance was greater than the estimated mean percent change for HDL cholesterol and luteinizing hormone, indicating that extent of degradation for these analytes did not exceed technical variation.


Despite evidence for systematic changes over long-term storage, correlations between baseline and later measures were high with little relation between size of the correlation and estimated mean difference across time points. QC experiments to assess the impact of long-term storage on anticipated analytes of interest are important in planning cohort studies with banked samples.

Acknowledgments:The authors thank Quest Diagnostics, Inc. for testing the samples, providing the results, and providing quality control variance data. We thank Kristie Dantzler for laboratory coordination of sample collection, storage, transfer, and returned results.

Conflicts of Interest and Source of Funding: Supported by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. The authors report no conflicts of interest.

Correspondence: Cynthia Kleeberger, 1007 Slater Road, Durham, NC 27703. Email: ckleeberger@s-3.com.

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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The Effects of Long-Term Storage on Commonly Measured Serum Analyte Levels

Researchers propose novel solution to minimize recurrent caries

When patients go to the dentist to fill a cavity, they’re trying to solve a problem — not create a new one. But many dental patients get some bad news: bacteria can dig under their tooth-colored fillings and cause new cavities, called recurrent caries.

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Researchers propose novel solution to minimize recurrent caries

High School Students First People in Arkansas to Successfully 3D Print a Brain Tumor

(L-R) Post-chemo tumor and pre-chemo tumor, 3D printed on a MakerBot 3D Printer.

We often hear about how 3D printed medical models can help surgeons plan out complex surgeries ahead of time, as well as being an educational tool for medical students. 3D printed tumor models are especially helpful, as they can be used to give doctors a much better idea of what they’ll be up against in the operating room; they can also be used to develop more effective cancer treatments. But 3D printed tumors can also help patients more fully understand what is going on inside their bodies as they prepare to undergo scary, complex surgeries.

I think Swedish songwriter and singer Jens Lekman put it best when he explained the concept behind his song “Evening Prayer,” which mentions a 3D printed tumor model.

“The idea of printing out something that’s as scary as a tumor into its concrete form was something that spoke to me – there is something very liberating about that idea,” Lekman said last year.

If a patient is nervous about a surgery to remove a tumor, it can help to physically hold the tumor model in their hands ahead of time, and also a point of triumph for them if they survive – look at this thing that used to be inside of my body, and I beat it.

Ella Pace and Madeline Scott present Nancy Foris with a replica of her brain tumor.

This is why high school students Ella Pace and Madeline Scott, part of the “EAST” program at Hot Springs World Class High School in Arkansas, wanted to 3D print a replica of a patient’s tumor for her post-surgery.

“You’re going through a serious situation, you don’t know what’s going on, it’s hard to understand,” said Pace, a freshman. “With the tumors, [patients] can become a bit more familiar with their situation.”

According to Stephanie Bennett of KATV, thanks to their tumor project, called Cerebral Studies, the two students have become the first people in the state to successfully 3D print a brain tumor.

The school district’s mission is to make sure that every student has the necessary skills and ethical standards of integrity to compete in society, while the high school gives them a positive climate to enhance their personal development and attain a high quality education and marketable skills.

EAST students Madeline Scott and Ella Pace. [Image: Hot Springs World Class High School EAST Program via Facebook]

Pace and Scott want to achieve real experience in the medical field, and had the opportunity to sit in on Nancy Foris’ brain surgery four months ago. After the experience, they decided to take it further and 3D print an exact replica of the tumor for Foris, in order to give her a psychological sense of empowerment. But they don’t want to stop after this tumor.

“At any age, finding out that you have cancer or a tumor in general–it’s scary. It’s hard to wrap your mind around,” explained Scott, who is a junior. “So if we can give them [patients] something to show them that ‘this is what’s in your head, this is what’s inside of you,’ it can give them a better sense of their current situation.”

The students are planning on using their newfound 3D printing skills in the pediatrics field, and have a goal of getting to the point where they are able to 3D print tumor replicas pre-surgery, to give patients a better understanding of what’s happening inside their bodies. Additionally, surgeons can better visualize the vascularity of tumors using 3D printed models.

Last week, the months-long project finally came to an end as Scott and Pace met Foris at the doctor’s office to present her with an exact 3D printed replica of the tumor that used to be inside her brain.

Scott and Pace worked with KATV’s Stephanie Bennett and Rachel Gilbride to document Cerebral Studies, their project that replicates tumors using 3D technology. [Image: Hot Springs World Class High School EAST Program]

Holding the tumor model in her hand, Foris said, “I was thinking it was maybe, [the size of a pinky], no, it’s a little larger than a pinky.”

Foris is glad to be alive, and grateful that the girls were so dedicated to the project. But the project was a difficult one to complete.

EAST Facilitator John Stokes said, “They have experienced failure; they have also experienced drastic success, and it better prepares them for the future.”

Pace and Scott aren’t done yet, and for the next step of their medical 3D printing journey, the two will be attending the Winter Clinics symposium for neurosurgeons, taking place next month in Colorado.

To see the inspirational story of the 3D printed brain tumor for yourself, check out the video on KATV.

Discuss this and other 3D printing topics at 3DPrintBoard.com or share your thoughts in the Facebook comments below. 

[Source: KATV]


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High School Students First People in Arkansas to Successfully 3D Print a Brain Tumor

Shapecrunch Allows Doctors and Consumers to Create 3D Printed Insoles

3D printing has made its mark in areas such as aerospace, with the creation of rocket components, igniters, and more. This progressive technology is allowing innovative automotive parts to be made for companies like Ford, BMW, and even Rolls Royce.

But we also spend a lot of time, it would seem, discussing what 3D printing can do for feet! From running shoes to high heels, designers and manufacturers have embraced the ability to prototype and manufacture futuristic products—and orthotic insoles have been a popular item also. Because they can be time consuming to order, as well as expensive, 3D printing is an attractive option for manufacturing such items. Not only can they be made quickly, but usually at a fraction of the price when compared to conventional insoles.

Now, Delhi-headquartered Shapecrunch is 3D printing custom insoles for individuals suffering from issues that are all-too-common such as problems stemming from diabetes, flat feet, and plantar fasciitis. The company was founded in 2015 by Nitin Gandhi, Jatin Sharma, Arunan Arivalagan, and Jiten Saini, inspired by the challenges Gandhi was having finding custom insoles for flat feet.

“I went to the doctor and he told me to get a pair of custom orthotics. Then I went to a shop to get those made and was surprised to see the manual process. All the machines were imported and the orthotics that I finally got had to be replaced because they were uncomfortable. Then again I had to go there,” Gandhi recalls.

Jiten Saini, Arunan Arivalagan, Nitin Gandhi and Jatin Sharma

On speaking with Gandhi’s doctor and doing their research, the group discovered that conventional equipment for creating such devices is considered to be very expensive, and only a few other companies or medical professionals were offering the service. With Gandhi and Sharma already experienced in 3D printing (and they are all engineers in varying fields), a light bulb went off.

“Since were already working in 3D printing, we thought how if we 3D print the insoles and see if it’s comfortable. It actually worked,” Gandhi says.

The Shapecrunch system is streamlined and completely digitized, requiring the doctor to scan the patient’s foot and enter the data. The software transfers the data into a 3D model which can then be 3D printed and shipped to the patient. Users without serious foot problems (and required medical care) can even scan their own feet and complete the process on their own.

“Our algorithm captures more than 1,000 points from feet and converts them into a 3D model,” Gandhi reveals.

Poron is the 3D printing material used by Shapecrunch, with soft cushioning added after the print is complete. The insoles are available in three different styles: sports, dress, and formal.

Currently, the Shapecrunch team works with the following medical professionals in providing them with the scanning technology:

  • Orthopedists
  • Physiotherapists
  • Chiropractors
  • Podiatrists

For a company who just put their product on the market last year, response has obviously been very positive with 1,200 patients using their services so far. Twenty percent have ordered a second pair of orthotics already too!

“The insoles are really comfortable. I use them in my running shoes and hiking shoes. They provide cushioning to my feet, which has reduced the pain and problems of swollen feet,” says Madhu Bhardwaj, a happy Shapecrunch customer.

The team trains doctors in how to use the Shapecrunch product, and then they are able to set up their own labs for less than $200.

“Shapecrunch allows us to provide full customization and helps us solve problems, which can’t be solved with traditional methods,” said Dr. Abhishek Jain, Founder of Delhi Foot.

More than 30 clinics are using Shapecrunch now, and the team has filed three patents for their product.

“…the biggest challenge for us was gaining knowledge of the foot and developing the algorithm, for which we worked with multiple foot specialists,” said Gandhi. “We first did basic trials with AIIMS, working with the PMR department. Later, the project got funded to do a bigger study.

“Most existing competitors use expensive imported machines for foot impression and require many people to fabricate the insole manually. With computer vision and machine learning we have digitized the whole process, disrupting the whole space.”

Shapecrunch currently has 10 members on their team, and while they are based in India, they have received orders from patients in Europe and the US. The new company spent their first year and a half doing research with All India Institute of Medical Sciences (AIIMS), New Delhi. They have also received a grant from BIRAC to continue doing clinical research with AIIMS. Along with that, the Shapecrunch team has also received an undisclosed amount of seed funding, with should offer a positive boost.

They hope to begin turning a profit this year, and plan to continue working on related products that will benefit runners as well as those suffering from complications due to diabetes.

Find out more about how the Shapecrunch system works here.

Let us know your thoughts; join the discussion of this and other 3D printing topics at 3DPrintBoard.com or share your thoughts below. 

[Source / Images: YourStory]


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Shapecrunch Allows Doctors and Consumers to Create 3D Printed Insoles