02 December 2022

Distrust in Supreme Court Climbs

Welcome back. About a month ago, I released a blog post, Americans Need Civics Class. The post highlighted the results of the Annenberg Public Policy Center’s Civics Knowledge Survey. Wrapping up the post, I mentioned that the center would soon publish the survey’s findings on the Supreme Court of the United States (SCOTUS).

The Supreme Court Building, west fa├žade (from www.britannica.com/event/Bollinger-decisions or see www.supremecourt.gov/about/courtbuilding.aspx).
Well, the findings appeared, but I hesitated. How affected would they be by the court’s overturning Roe v. Wade two months before the survey was conducted. I finally decided it didn’t matter. SCOTUS has survived many controversial decisions over the years (e.g., modifying the Voting Rights Act of 1965 in 2013, reversing century-old campaign finance restrictions in 2010 with Citizens United, Roe v. Wade in 1973).

So here we go. As a reminder, the national survey of 1,113 U.S. adults was conducted by phone by the research company SSRS August 2-13, 2022. It has a margin of error of ± 3.6% at the 95% confidence level.

Survey Highlights

Disapproval: 53% of respondents disapprove of how SCOTUS is handling its job; Democrats, 76%, Republicans, 25%. 

Question: How much do you approve or disapprove of the way SCOTUS is handling its job? Independents, other party, or no party (modified from cdn.annenbergpublicpolicycenter.org/wp-content/uploads/2022/10/Appendix_APPC_SCOTUS_Oct_2022.pdf).
Distrust: 53% of respondents have little or no trust in SCOTUS to operate in the best interests of American people; Democrats 68%, Republicans, 29%; total distrust up from 31% in 2019.

Question: How much do you trust SCOTUS to operate in best interests of the American people? (modified from cdn.annenbergpublicpolicycenter.org/wp-content/uploads/2022/10/Appendix_APPC_SCOTUS_Oct_2022.pdf).
Decisions: 40% of respondents say SCOTUS justices set aside personal and political views and make rulings based on the constitution, law and facts; Democrats 29%, Republicans, 55%; total down from 59% in 2021.

Question: Do you think SCOTUS justices set aside personal and political views and make rulings based on constitution, law and facts? (modified from cdn.annenbergpublicpolicycenter.org/wp-content/uploads/2022/10/Appendix_APPC_SCOTUS_Oct_2022.pdf).
Conservative or Liberal: 49% of respondents think SCOTUS is sometimes liberal, sometimes conservative depending on the law and facts of the case; down from 63% in 2019.

Power: 54% of respondents feel SCOTUS has about the right amount of power; down from 70% in 2019, but up from 48% in 2013.

Politics: 69% of respondents strongly or somewhat agree that SCOTUS gets too mixed up in politics; 28% disagree.

Number of Justices: 38% of respondents strongly or somewhat oppose increasing the number of justices, 30% strongly or somewhat favor increasing the number of justices, and 32% have no opinion.

Wrap Up
Overall, the Supreme Court took a bit of a hit, mainly from Democrats, presumably responding to Roe v. Wade being overturned with the Dobbs v. Jackson decision.

On that specific issue, 58% of survey respondents strongly or somewhat disapprove of the decision that the Constitution does not guarantee a right to abortion and that abortion laws can be set by each state; 39% strongly or somewhat approve.

Thanks for stopping by.

P.S.
Annenberg Constitution Day Civics Survey: www.annenbergpublicpolicycenter.org/political-communication/civics-knowledge-survey/
Supreme Court survey methodology and results: cdn.annenbergpublicpolicycenter.org/wp-content/uploads/2022/10/Appendix_APPC_SCOTUS_Oct_2022.pdf
Article on Supreme Court survey on EurekAlert! website: www.eurekalert.org/news-releases/967308

25 November 2022

Multivitamin Trials

Welcome back. Several years ago, in a blog post, Canned Fish for Lunch, I wrote that although my diet is nutritionally impressive, I still take a multivitamin. I acknowledged that research has shown little or no benefit and that if one’s diet is well balanced, there’s probably no need for any dietary supplement. Nevertheless, I figured it can’t hurt.

Warren’s dietary supplements: multivitamin, vitamin C and calcium-vitamin D (from
Canned Fish for Lunch).
Oh, it’s not just me. Preceding my blog post by a few years, a national survey found that half of U.S. adults took at least one dietary supplement during a 30-day period. Multivitamins topped the list. The most commonly cited reason was for overall health and wellness and to fill nutrient gaps in the diet.

Bringing it up to date, a systematic review of 84 studies of dietary supplements found not much has changed regarding cardiovascular disease or cancer prevention. But surprise, surprise, there may be other benefits. Another recent study found that a daily multivitamin might improve cognition in older adults or protect cognitive health with age.

I’ll begin with the systemic review then move on to the cognitive health study.

The Systematic Review
The U.S. Preventive Services Task Force (USPSTF) is an independent (i.e., non-governmental), volunteer panel of national experts in disease prevention and evidence-based medicine. The Task Force works to improve the health of people nationwide by making evidence-based recommendations about clinical preventive services.

U.S. Preventive Services Task Force logo (from www.uspreventiveservicestaskforce.org/uspstf/).

Among a wide variety of subjects addressed over the years, the USPSTF provided the recent recommendations on dietary supplements to prevent cardiovascular disease and cancer as well as recommendations in 2003 and 2014.

For the 2022 recommendations, the USPSTF commissioned a team of researchers affiliated with Kaiser Permanente and Oregon Health & Science University to complete an evidence report and systematic review.

The USPSTF’s Recommendation Statement as well as the researchers’ evidence report and systematic review were both published in the 21 June issue of the Journal of the American Medical Association (JAMA).

As regards multivitamins for community-dwelling, nonpregnant, generally healthy adults, the USPSTF concluded: [T]he evidence is insufficient to determine the balance of benefits and harms of supplementation with multivitamins for the prevention of cardiovascular disease or cancer. Evidence is lacking and the balance of benefits and harms cannot be determined. The conclusion was consistent with the 2014 Recommendation Statement.

Multivitamin for Cognition
The study, COSMOS-Mind, was conducted by researchers affiliated with Wake Forest University School of Medicine, Brigham and Women's Hospital, Harvard Medical School and Harvard T.H. Chan School of Public Health.

COSMOS-Mind (COcoa Supplement and Multivitamin Outcomes Study of the Mind) was an ancillary study to a much larger, longer term study (graphic from www.whi.org/md/news/cosmos-mind-results).

Their study design was based on two findings:
(1) Normal brain function requires various vitamins, minerals and other nutrients, yet clinical trials of the effects of individual nutrients on cognition have yielded mixed results.
(2) Earlier research, mostly observational, has suggested that flavanols--compounds found in high levels in unprocessed cocoa--might benefit cognition (e.g., see 2014 and 2012 blog posts Chocolate for Health and Sleep and Memory).

For the study, participants were given a daily cocoa extract and/or multivitamin-mineral supplement, or a placebo, for three years. They completed a battery of cognitive tests over the phone at the beginning of the study and once a year afterward. Of the 2,262 participants initially enrolled (mean age 73 yr, 60% female), 92% completed the baseline and at least one annual assessment.

The study found no difference in global cognition between those who took cocoa extract and those who did not. Participants who took the multivitamin, however, had higher global cognition scores. Significant improvements in memory and executive function were also observed with daily multivitamin but not with the cocoa extract.

While the results suggest that a daily multivitamin-mineral supplement might improve cognition in older adults or protect cognitive health with age, the researchers caution that the results are still preliminary.

Wrap Up
So, should you take a multivitamin if your diet is well balanced? Your call. As for other vitamin and mineral supplements, you might take a look at the Evidence Report and Systematic Review or USPSTF’s Recommendation Statement. For most, there was little evidence of serious harms with recommended doses.

Stay safe, be well and thanks for stopping by.

P.S.
National survey of dietary supplement use in Nutrients journal: www.mdpi.com/2072-6643/10/8/1114/htm
USPSTF: www.uspreventiveservicestaskforce.org/uspstf/
USPSTF Final Recommendation Statement: www.uspreventiveservicestaskforce.org/uspstf/recommendation/vitamin-supplementation-to-prevent-cvd-and-cancer-preventive-medication#bootstrap-panel--14--content
USPSTF Recommendation Statement in JAMA: jamanetwork.com/journals/jama/fullarticle/2793446
Updated Evidence Report and Systematic Review in JAMA:
jamanetwork.com/journals/jama/fullarticle/2793447
USPSTF Recommendation in 2014 in Annals of Internal Medicine journal:
pubmed.ncbi.nlm.nih.gov/24566474/
COSMOS-Mind study of cocoa and daily multivitamin for cognition in Alzheimers & Dementia journal: alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12767

18 November 2022

Genetics, Aging and Environment

 “Age is just a number and mine is unlisted,” says the actor in the TV commercial for the high protein nutritional drink. We age differently, so some might count age as only a number. But don’t rush to discount age. A recent study showed age often plays a greater role than genetics in gene expression and susceptibility to disease.

TV commercial in which actor says, “Age is just a number and mine is unlisted” (from www.ispot.tv/ad/nHX8/boost-high-protein-age-is-just-a-number).

Welcome back. Let me jump right in with the oldest evolutionary explanation for biological aging. On 6 December 1951, Peter Brian Medawar presented an inaugural lecture at University College, London, titled “An Unsolved Problem of Biology.” He proposed the mutation accumulation theory of aging.

Medawar’s theory is based on the idea that the force of natural selection ebbs with age as individuals are less likely to reproduce and contribute their genetic information to the next generation. As reproduction ceases, the weaker force of natural selection cannot consistently eliminate harmful mutations, which then accumulate and lead to the evolution of aging.

Genetics vs. Aging
Now, let me jump to the recent study I mentioned in the opening. A team of researchers affiliated with the University of California, both Berkeley and Los Angeles, investigated the relative effects of genetics, aging and environment on how some 20,000 human genes are expressed. The researchers built a statistical model using data on 27 different human tissues available from nearly 1,000 people. (If you’re feeling a bit lost about tissues and genes, “Tissues” under P.S. below might help.) 

Four types of tissue (graphic prepared by A.D.A.M Images; figure from medlineplus.gov/ency/imagepages/8682.htm).
The team found that genetics mattered about the same amount across the tissues, not playing more of a role in one tissue or another.

The impact of aging, however, varied more than twentyfold among the tissues. Whether blood, colon, arteries, esophagus or fat tissue, age plays a much stronger role than genetics in driving gene expression patterns.

Outlier Tissues
The researchers also found that Medawar’s theory did not hold for all 27 tissues. Evolutionary important genes were expressed at higher levels in older people in five types of tissues. What’s different about these tissues is that they constantly turn over throughout our lifespan. Because blood, for instance, has to proliferate for us to live, these genes have to be turned on late in life.

Every time these tissues replace themselves, they risk creating a genetic mutation that can lead to disease. And these five tissues do produce the most cancers.

Trends in Cancer: the evolution of lifespan and age-dependent cancer risk (from
www.cell.com/trends/cancer/fulltext/S2405-8033(16)30121-2
).
 

The study indirectly indicated the effect of environment--air, water, food, exercise; the impact of everything other than age and genetics. The researchers judged that environment accounts for up to one-third of the changes in gene expression with age.

Wrap Up
The results underscore that, while our genetic makeup can help predict gene expression when we are younger, it is less useful in predicting which genes are ramped up or down when we’re older (being older than 55 in the study). Identical twins have the same set of genes, yet as they age, their gene expression profiles diverge, and the twins can age very differently from one other.

The findings have implications for efforts to correlate diseases of aging with genetic variation. The study’s senior researcher suggests that perhaps these efforts should focus less on genetic variants that impact gene expression when pursuing drug targets.

So, give age due diligence, and thanks for stopping by.

P.S.
Mutation accumulation theory of aging
books.google.com/books/about/An_Unsolved_Problem_of_Biology.html?id=ozEmPQAACAAJ
en.wikipedia.org/wiki/Mutation_accumulation_theory
Study of tissue impacts of aging and genetics in Nature Communications journal: www.nature.com/articles/s41467-022-33509-0
Article on study on EurekAlert! website: www.eurekalert.org/news-releases/967253

Tissues (from medlineplus.gov/ency/imagepages/8682.htm and training.seer.cancer.gov/anatomy/cells_tissues_membranes/tissues/)
Cells are the building blocks of all living things, and genes are inside almost every cell in our bodies. Tissues are groups of cells that have similar structure and that function together as a unit. There are four basic types of tissue: connective tissue supports other tissues and binds them together (bone, blood and lymph tissues); epithelial tissue provides a covering (skin, the linings of passages inside the body); muscle tissue includes striated muscles that move the skeleton and smooth muscle, such as the muscles that surround the stomach; nerve tissue is made up of nerve cells (neurons) and carry "messages" to and from parts of the body.

11 November 2022

Justifying Drug Prices

Pharmaceutical companies and their trade groups have opposed numerous proposals aimed at lowering drug prices. They argue that high drug prices are needed to recover research and development investments. This blog post reviews a study that essentially refutes that argument. Before you read the post and possibly become irate, realize the study has significant limitations.

Welcome back. In case you haven’t heard, the USA wins the prize for the world’s highest prices for new medicines. What’s more, the prices of many therapeutic agents have increased at rates far exceeding the rate of inflation.

The Inflation Reduction Act that President Biden signed into law in August includes provisions to reduce prescription drug costs. Not to complain, but the law only covers those on Medicare and certain prescription drugs. And it doesn’t kickoff until 2026.

In a recent study, researchers with the London School of Economics and Political Science, University of Pittsburgh and University of California, San Diego set out to determine if there is an association between how much drug companies spend on research and development (R&D) of new drugs and how much they charge for those drugs. They reasoned that there should be some positive association if high drug prices are truly justified by high R&D costs.

Drug companies blame high drug prices on the cost of research and development (graphic from multiple websites and from earlier blog post, Drug Safety).

Relating Drug Prices to R&D Costs
The analysis focused on 60 drugs approved by the Food and Drug Administration from 2009 to 2018. Data on R&D investments and list or net prices for these drugs were available from the SSR Health database.

Drug Companies' Investments  The amount spent to bring each drug to market followed investor reports. Phase-specific clinical trial success rates were used to estimate the amount spent on failed trials for other drug candidates, with a capital rate cost of 10.5% per year. The estimates thus accounted for the amount spent to develop the products in question as well as for the probability of failure in the drug industry and costs associated with acquiring funds from investors. Product list and net prices were from SSR Health.

The five critical steps in drug development (from www.nebiolab.com/drug-discovery-and-development-process/).
Consumer Costs  Calculating the number of units needed for treatment assumed a standard dose according to the package label of each drug, grouped into acute, chronic and cyclical treatment categories. Total costs were estimated separately using list and, if available, net prices obtained from SSR Health at the time of launch and in 2021.

Analyzing the Association  To test the association between R&D investments and treatment costs, correlation coefficients were estimated and linear regression models were fitted that controlled for other factors associated with treatment costs. Two models were used: one that adjusted for all variables associated with treatment costs and a second which excluded highly correlated variables.

Results  Neither correlations nor regression models showed any association between estimated R&D investments and treatment costs based on list prices at launch or net prices one year after launch. This result held when 2021 prices were used to estimate treatment costs.

Wrap Up
Among the key limitations reported by the researchers were the small number of drugs (only 60) due primarily to the lack of publicly available data, the difficulty of tracking all preclinical company investments, and the difficulty of isolating R&D costs for any one product given possible spillover in knowledge and resources from other efforts.

The researchers note that the lack of association between R&D investments and drug prices was not unexpected, since pharmaceutical firms aim to maximize profits based on consumers’ willingness to pay. They conclude that, if drug companies continue to justify high drug prices with the R&D investments, they should supply additional data to support the claim. Do you think they will? 

Top 10 global pharmaceutical companies by revenue, 2021 (from pharmaboardroom.com/articles/top-10-global-pharma-companies-2021/).
 Thanks for stopping by.

P.S.
Prescription Drug Provisions in the Inflation Reduction Act: www.kff.org/medicare/issue-brief/explaining-the-prescription-drug-provisions-in-the-inflation-reduction-act/
Study of associating new drug investment with treatment costs in JAMA Network Open: jamanetwork.com/journals/jamanetworkopen/fullarticle/2796669
Article on study on EurekAlert! website: www.eurekalert.org/news-releases/965981
SSR Health: www.ssrhealth.com/

04 November 2022

Computer Eye Breaks

Welcome back. Have you ever heard of the 20-20-20 rule? I hadn’t. Apparently, taking a break of at least 20 seconds, every 20 minutes, to look at least 20 feet away has long been recommended as a way of easing eye strain when staring at a computer display. 

20-20-20 rule break reminder issued by software screen (Fig 2, www.contactlensjournal.com/article/S1367-0484(22)00199-0/fulltext).

I came upon the rule because a recent study confirmed that adopting the guideline does indeed help ease some symptoms of prolonged computer use. The study, conducted by a team of researchers affiliated with Spain’s University of Valencia, Slovakia’s Slovak University of Technology in Bratislava, and the UK’s Aston University, was the first to properly validate the rule.

Digital Eye Strain
Long sessions at the computer have been associated with eye and vision problems generally labeled “computer vision syndrome” or “digital eye strain.” It’s estimated that at least half of the people using computers in their regular work have some form of digital eye strain. The symptoms fall into two categories:

External symptoms, related to dry eye, include burning, irritation, dryness, tearing, foreign body sensation, sensitivity to bright lights and discomfort.

Internal symptoms, linked to accommodative or binocular vision stress, include eye strain, eye ache, headache, diplopia, blurred vision and difficulty in refocusing.

Study Elements
Participants The researchers enlisted 29 volunteers for the controlled clinical study. Inclusion criteria were digital eye strain determined by a standard questionnaire, best-corrected distance visual acuity at least 20/30 in both eyes, and computer use of a minimum of 4 hr/day, at least 5 days/week. (The average computer use reported by the participants was 7±2 hr/day, 6±1 days/week.)

Software A software application (https://www.blinkingmatters.com/) was modified to use each participant’s laptop computer webcam to assess user breaks, eye gaze and blinking and emit 20-20-20 rule reminders.

Eye blink and gaze detection software testing; the green square indicates the user is looking at the screen (Fig 1, www.contactlensjournal.com/article/S1367-0484(22)00199-0/fulltext).
Testing
Over the course of four visits one or two weeks apart, the researchers screened participants, installed the software onto participants’ laptops and instructed participants in the use of the 20-20-20 rule reminders. They also conducted two weeks of measurement sessions of about 45 minutes in the same laboratory, the same day of the week, from 9 to 11 a.m., under the same environmental conditions (temperature and humidity).

Digital eye strain, binocular vision and dry eye were assessed before and after two weeks of using the reminders and one week after discontinuing. These included symptom questionnaires, a full suite of binocular measurements (visual acuity, accommodative posture, stereopsis, fixation disparity, ocular alignment, accommodative facility, positive/negative vergences and near point of convergence), and dry eye sign assessments (tear meniscus height, conjunctival redness, blink rate and incomplete blinking, lipid layer thickness, non-invasive keratograph break-up time, corneal and conjunctival staining and lid wiper epitheliopathy).

Results

With the 20-20-20 reminders operating, the participants spent less time on computer work. Although they took more breaks, the length of breaks decreased.

The only change to any binocular parameter after the management period was an increase in accommodative facility. Dry eye symptoms and digital eye strain decreased with the rule reminders, though that improvement was not maintained after the rule reminders ended. There were no changes on any ocular surface and tear film parameter with the rule reminders.

Data collected by study software before and after activation of 20-20-20 rule reminders with mean ± SD, min – max; min=minutes; ms=milliseconds, a-intra-average values. (Modified from Table 2, www.contactlensjournal.com/article/S1367-0484(22)00199-0/fulltext).
Wrap Up
The researchers concluded that the 20-20-20 rule is an effective strategy for reducing digital eye strain and dry eye symptoms; however two weeks was not long enough for significant improvement in binocular vision or dry eye signs.

I suspect that most of us learned long ago to look away and even get up from the computer, we just don’t do it enough. Maybe the catchy rule moniker will help.

Thanks for stopping by.

P.S.
Study of testing the 20-20-20 rule in Contact Lens and Anterior Eye journal: www.contactlensjournal.com/article/S1367-0484(22)00199-0/fulltext
Computer vision syndrome questionnaire: www.sciencedirect.com/science/article/abs/pii/S0895435615000232
Dry eye questionnaire: okeyecare.com/wp-content/uploads/2020/12/OkotoksEyecare-DEQQuestionaire-Fillable-1.pdf
Articles on study and topic on EurekAlert! and American Optimetric Assoc. websites:
www.eurekalert.org/news-releases/965502
www.aoa.org/healthy-eyes/eye-and-vision-conditions/computer-vision-syndrome