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Published on Leave a comment on What Did the Chronic Sinusitis Study Really Show?

Just read a small study that compared the microbes in the sinus microbiome between 12 healthy people with no sinusitis (controls) and 14 with chronic sinusitis, their neurotransmitter levels (serotonin, dopamine, and GABA), and also looked at depression scores in the 2 groups. Well, of course they found some microbial differences between healthy people and those with chronic rhinosinusitis (CRS), but they also found that those with the most severe chronic sinusitis tended to have the most depressive symptoms, and lower amounts of the neurotransmitters studied, but they did not find significant differences overall.

I found their summary and conclusions problematic, since they discussed that "possibly" the sinus microbes influence brain neurotransmitters. And they pointed out that as certain disease associated microbes increased (especially Moraxella), the neurotransmitter concentrations tended to decrease in those with sinusitis. But since there were no significant group differences, they did not prove their hypotheses, and conclusions can not be made. So saying there is "the potential for downstream effects of the sinonasal microbiota on neural signaling and, subsequently, brain function and behavior" is misleading and overreaching. The researchers also said it was "difficult to discern disease associations from natural variation." Hah!

It should be obvious that the worse the chronic sinusitis, the more depressive symptoms, because having chronic sinusitis is DEPRESSING. One suffers with it. Some people have told me how chronic sinusitis has destroyed their life - whether their health, financially, with relationships, etc. Of course they will have higher depressive scores! And when a Lactobacillus sakei product or other probiotic successfully treats sinusitis (usually very quickly), then the mood is one of elation as symptoms go away (finally health!).

All one can say (based on studies) is: the sinus microbiomes in healthy people (normal sinus microbial community) are somewhat different from those with chronic sinusitis (out-of-whack microbial community or dysbiosis). And one would expect that those with less severe/milder sinusitis have a "better" community of sinus microbes - that is, more microbes that are associated with health, and fewer of those associated with sickness, than sicker people. Which is what this study suggested. Excerpts from the International Forum of Allergy & Rhinology:

The sinonasal microbiota, neural signaling, and depression in chronic rhinosinusitis

The complex relationships between the human microbiota, the immune system, and the brain play important roles in both health and disease, and have been of increasing interest in the study of chronic inflammatory mucosal conditions. We hypothesized that the sinonasal microbiota may act as a modifier of interkingdom neural signaling and, subsequently, mental health, in the upper respiratory inflammatory condition chronic rhinosinusitis (CRS). In this study we investigated associations between the sinonasal microbiota; local concentrations of the neurotransmitters serotonin, dopamine, and γ-aminobutyric acid (GABA); and depression severity in a cohort of 14 CRS patients and 12 healthy controls.

Several commonly “health-associated” sinonasal bacterial taxa were positively associated with higher neurotransmitter concentrations and negatively associated with depression severity. In contrast, several taxa commonly associated with an imbalanced sinonasal microbiota negatively associated with neurotransmitters and positively with depression severity. Few significant differences were identified when comparing between control and CRS subject groups, including neurotransmitter concentrations, depression scores, or sinonasal microbiota composition or abundance. Conclusion: The findings obtained lend support to the potential for downstream effects of the sinonasal microbiota on neural signaling and, subsequently, brain function and behavior.

SOME OTHER EXCERPTS: Depression scores were also not significantly different between controls and CRS patients. .... The serotonin levels in CRS patients compared with control subjects tended to be lower, but not significantly so. Although median values for dopamine, GABA, and serotonin were generally lower in CRS patients than controls, all 3 neurotransmitters had a greater range among those with CRS, and no differences were significant. ... For both CRS and control individuals, bacterial communities were generally dominated by OTUs of the genera Corynebacterium and Staphylococcus.

Correlation analyses identified associations between members of the genera Staphylococcus, Finegoldia, Propionibacterium, Peptoniphilus, and Anaerococcus, as well as bacterial community diversity overall. Members of these genera have been previously identified as representative of more “health-associated” sinonasal bacterial community types, whereas their depletion has been associated with lower bacterial community diversity, increased bacterial load, increased rates of asthma, and elevated markers of inflammation. Similarly, members of the genera Burkholderia and Propionibacterium have been identified as 2 potential “gatekeepers” that help maintain bacterial community stability in the sinonasal tract. In the present study, several of these same bacterial taxa were significantly positively correlated with neurotransmitter levels and negatively with depression severity, whereas several other OTUs (including members of Streptococcus, Rothia, Enterobacteriaceae, Corynebacterium, and Moraxella) showed the opposite pattern (negatively associated with neurotransmitter levels and positively with depression severity). 

Published on Leave a comment on Vigorous Physical Activity Linked To Lower Death Risk In Older Women

The message is clear from a recent study: older adults should get out and move, move , move (brisk walking is fine) - to lower the risk of early death. The older women engaging in the most moderate to vigorous activity had a 65% lower risk of early death during an average follow-up period of 2.3 years (when compared to the women with the least exercise).

How much exercise did the groups get? The least active had 6.8 minutes per day of moderate to vigorous exercise, and the most active had about 68 minutes/day of moderate to vigorous physical activity. The women wore a Fitbit type of device (an accelerometer) that measured their movements. Moderate to vigorous exercise was any movement that got the heart rate up a bit, made them sweat a little - and which could be brisk walking.

The study was done with older women (in their 70s), but one would think it also applies to men. Note: all-cause mortality means death from any cause (death in general). From Medscape:

Intense Exercise Tied to 65% Lower Death Risk in Older Women

Older women who engaged in the greatest amount of moderate to vigorous physical activity, such as brisk walking, were found to have a 65% lower risk of all-cause mortality compared with women who performed the least amount of such exercise, a new study reports. The researchers examined women in their early 70s in the Women's Health Study (WHS) who wore a triaxial accelerometer for 7 days to measure physical activity. The findings, by Dr I-Min Lee (Brigham and Women's Hospital, Boston, MA) and colleagues, were published November 6, 2017 in Circulation.

It's been known for a long time that physical activity is associated with lower mortality rates, Dr Lee told theheart.org | Medscape Cardiology.... Now that physical activity can be better measured using a research-grade triaxial accelerometer, the magnitude of the reduced risk of short-term death with recommended amounts of moderate to vigorous physical activity can be seen to be as strong as not smoking, Lee said. ... This study "reinforces the message that adults should strive to meet physical activity guidelines of 150 minutes of moderate or 75 minutes of vigorous exercise per week," Dr Alpa Patel (American Cancer Society, Atlanta, Georgia) who recently published a related article that showed benefits from walking told theheart.org | Medscape Cardiology.

From 2011 to 2015, 18,289 of 29,494 living women (63%) in the Women's Health Study agreed to participate in the current study.... The remaining 17,708 women were mailed a research-grade triaxial accelerometer (ActiGraph GT3X+, ActiGraph Corp) and asked to wear it on their hips for 7 days (but to take it off when sleeping or swimming) and then mail it back. 

The women spent a median of 8.4, 5.8, and 0.5 hours/day being sedentary, doing light physical activity, and doing moderate to vigorous physical activity, respectively. "The least active quartile were doing 8 minutes a day of moderate to vigorous . . . physical activity," Lee said, which was typically "brisk walking, anything that gets your heart rate up a little bit, gets you to sweat a little bit." The most active quartile did about 68 minutes/day of moderate to vigorous physical activity. During an average follow-up of 2.3 years, 207 women died. The total amount of physical activity was inversely related to the risk of all-cause mortality during follow-up, after adjustment for age and time spent wearing the device. 

Published on Leave a comment on Pesticide Residues In Our Food Are Increasing

It looks like pesticide residues are increasing in our food. Not good, especially since we don't know what chronic low-levels of these residues do to us. And remember, we're exposed to mixtures of these residues daily, not just one at a time.

The only way to reduce exposure to these pesticide residues, including the controversial and widely used pesticides 2,4-D and glyphosate, is by eating organic foods. [See all posts on PESTICIDES for more on their effects and concerns.] Excerpts from an article by journalist Carey Gillam in Environmental Health News:

Hold the plum pudding: US food sampling shows troubling pesticide residues

New data released recently by the Food and Drug Administration (FDA) shows a rise in the occurrence of pesticide residues detected in thousands of samples of commonly consumed foods. Documents obtained from the agency through Freedom of Information Act (FOIA) requests also show the government is bracing for more, with the use of at least one controversial weed killing chemical – the herbicide known as 2,4-D - expected to triple in the next year.

And buried deep within the FDA's latest annual pesticide residue report is data showing that a controversial insecticide called chlorpyrifos, which is marketed by Dow Chemical and is banned from household use due to known dangers, was the fourth-most prevalent pesticide found in foods out of 207 pesticides detected.

Overall, about 50 percent of domestic food and 43 percent of imported foods sampled showed pesticide residues in the FDA's testing for fiscal year 2015, which is the period covered in the new report. That is up from about 37 percent of domestic and 28 percent of imported foods found with residues in 2010, and up from 38.5 percent and 39 percent, respectively, found by FDA a decade earlier in 2005.

FDA sampling has been shrinking over the years, dropping about 25 percent from a decade ago from more than 7,900 samples to 5,989 samples tested in its latest report. The U.S. Department of Agriculture also does annual pesticide residue testing, but looks at more than 10,000 samples. The latest USDA residue report, which also was for the 2015 time period, found about 85 percent of samples contained pesticide residues.

Notably, samples of fruits and vegetables – considered healthy food choices – showed the highest frequency of pesticide residues in the new FDA report. Roughly 82 percent of domestic American fruits and 62 percent of domestic vegetables carried residues of weed killers, insecticides and other pesticides commonly used by farmers.

Looking at imported fruits and vegetables, the FDA found that roughly 51 percent of imported fruits and 47 percent of imported vegetables carried residues. Overall, the imported foods had more illegally high levels of pesticide residues than did domestic foods sampled. More than 9 percent of both imported fruits and vegetables were considered in violation of legal pesticide residue limits compared to only 2.2 percent of American-grown fruits and 3.8 percent of domestic vegetables. 

The Environmental Protection Agency sets legal limits, referred to as "maximum residue limits" (MRLs) for pesticide residues on foods. The FDA and USDA routinely assure consumers that if residues are below the established MRLs, they are both legal and safe. But many scientists and medical professionals disagree, saying regulatory methods are outdated and too dependent on input from the chemical industry players selling the pesticides. 

Separate from the FDA's published residue report, internal FDA documents show the agency working to get a handle on the residues of two widely used herbicides - glyphosate and 2,4-Dichlorophenoxyacetic acid (2,4-D). An internal memo dated in May of this year obtained through FOIA states that 2,4-D use is "expected to triple in the coming year" because of new genetically engineered crops designed to tolerate direct application of the herbicide. Neither FDA nor USDA has routinely tested for glyphosate despite the fact it is the world's most widely used herbicide, and testing by academics, consumer groups and other countries has shown residues of the weed killer in food.

Published on Leave a comment on No Benefit From Some Probiotics or Xylitol in Treating Sore Throats

Shucks... A randomized controlled trial (the best kind of study) found that probiotics and xylitol did NOT help sore throat symptoms. Sore throats are medically known as pharyngitis. Xylitol is a birch sugar that causes local “bacterial interference” by inhibiting bacterial growth and the adherence of bacteria to the pharyngeal wall (the throat). The probiotics (beneficial bacteria) that they tested were strains of  Lactobacillus acidophilus, Bifidobacterium bifidum, and Bifidobacterium animalis. They also tested sorbitol chewing gum, which does not have any antiviral or antibacterial properties. Not one of these alone or combined had any effect on sore throat symptoms.

My take on this: perhaps other species of probiotics might help - maybe yes, maybe no. Just testing 3 strains of bacteria is too soon to rule out probiotics. This view is based on our (and others) experiences with chronic sinusitis - that it takes very specific bacteria species (especially Lactobacillus sakei) to treat sinusitis, and just taking some random strains may not help at all. From Science Daily:

New RCT shows no benefit from probiotics, xylitol chewing gum in alleviating sore throats

The use of probiotics and xylitol chewing gum to alleviate sore throat symptoms -- as an alternative to antibiotics -- appears to have no effect, according to a randomized controlled trial (RCT) published in CMAJ (Canadian Medical Association Journal).

Evidence exists that indicates probiotics and xylitol, a birch sugar that prevents bacterial growth, can help reduce recurrence of upper respiratory tract infections.

The study included 934 people in the UK during the four year study period (June 2010 to 2014), of whom 689 provided complete data for the trial. Using a symptom diary, participants reported the number of probiotic capsules and sticks of chewing gum used each day, as well as the severity of symptoms. They were study "compliant" if they had taken 75% of their allotted treatment.

Researchers found no significant effect of either probiotics or xylitol on sore throat (pharyngitis) symptoms. "There were no significant differences between groups for both the xylitol and the probiotic groups, which suggests that neither intervention helped in controlling acute symptoms," the authors write. [Original study.]

 Sore throat. Credit: Wikipedia

Published on Leave a comment on Fetus, Science, Evidence

The words and phrases science-based, evidence-based, fetus, and vulnerable are all important words in science and medicine, and are frequently used on this site when I post about new health studies. Medical treatment is based on science, and it is evidence-based (that's why studies are done - to test hypotheses, and to see what the evidence shows). The effects of viruses (e.g. Zika virus, measles), nutrition, and environmental pollutants (e.g. BPA, lead, mercury, pesticides, air pollution) all have effects on the developing fetus. Fetuses, children, the elderly, and immunocompromised individuals are all especially vulnerable to the effects from pollutants. See how important and powerful those words are?

The Washington Post reported Friday (December 15, 2917) that the Trump administration is prohibiting officials at the Centers for Disease Control and Prevention (CDC) from using a list of 7 words or phrases in official documents when preparing next year's budget proposals. The seven words are: science-based, evidence-based, fetus, vulnerable, diversity, transgender, and entitlement.

The CDC is the nation's top health agency and staffed with many scientists working on diseases throughout the world, including the Zika virus (which has an effect on the developing fetus),  and working on ways to prevent sexually transmitted diseases among transgender people. This is an agency with more than 12,000 employees and a $7 billion budget that works on all sorts of health issues - including food and water safety, heart disease and cancer, antibiotic resistance, and censorshipways to prevent epidemics. Their work is based on science, and it looks at all the evidence. Yup - those pesky words are an integral part of the function of the CDC, and of science..

Of course scientists are outraged by this censorship of science. So should you.

Published on Leave a comment on Lyme Disease Bacteria Can Survive After Treatment

A new study provides evidence for what so many people complain about - that after being treated for Lyme disease with several weeks of antibiotics - they feel that they are not cured, but instead still suffer from Lyme disease. Lyme disease is caused by the bacterium Borrelia burgdorferi, which is transmitted to a person during a tick bite. 

However, many medical professionals deny that a person can still have Lyme disease after antibiotic treatment, and instead call the lingering symptoms post-treatment Lyme disease syndrome (PTLDS). It is thought that between 10 to 20% of persons treated with antibiotics for Lyme disease have symptoms of PTLDS.

Hah! The Tulane University researchers found that yes, the live bacteria (B. burgdorferi spirochetes) can still be there in different organs of the body even after 28 days of antibiotic treatment. They studied late Lyme disease in both treated (with antibiotics) and untreated rhesus macaques - primates in which Lyme disease has effects similar to humans. Other studies have also found that the Lyme disease bacteria can evade treatment (here and here). From Medical Xpress:

Lyme bacteria survive 28-day course of antibiotics months after infection

Bay Area Lyme Foundation, a leading sponsor of Lyme disease research in the US, today announced results of two papers published in the peer-reviewed journals PLOS ONE and American Journal of Pathology, that seem to support claims of lingering symptoms reported by many patients who have already received antibiotic treatment for the disease. Based on a single, extensive study of Lyme disease designed by Tulane University researchers, the study employed multiple methods to evaluate the presence of Borrelia burgdorferi spirochetes, the bacteria that cause Lyme disease, before and after antibiotic treatment in primates.  ...continue reading "Lyme Disease Bacteria Can Survive After Treatment"

Published on Leave a comment on Some Common Traits of People Living to 100

What does it take to live to 100 in relatively good health? Are there common psychological traits? A study looked at 29 rural Italians aged 90 to 101 and their 51 younger family members to try to answer that question. They found that the elderly  participants had worse physical health but better mental well-being than their younger family members.

The older adults had a positive attitude or positivity (resilience and optimism), they worked hard, and had strong bonds with family and religion. They also had a strong need for control (family members called them "domineering") and a love of the land. The researchers summarized: "Exceptional longevity was characterized by a balance between acceptance of and grit to overcome adversities along with a positive attitude and close ties to family, religion, and land, providing purpose in life." From Science Daily:

Common psychological traits in group of Italians aged 90 to 101

In remote Italian villages nestled between the Mediterranean Sea and mountains lives a group of several hundred citizens over the age of 90. Researchers at the University of Rome La Sapienza and University of California San Diego School of Medicine have identified common psychological traits in members of this group. The study, publishing in International Psychogeriatrics, found participants who were 90 to 101 years old had worse physical health, but better mental well-being than their younger family members ages 51 to 75.

"The main themes that emerged from our study, and appear to be the unique features associated with better mental health of this rural population, were positivity, work ethic, stubbornness and a strong bond with family, religion and land." There were 29 study participants from nine villages in the Cilento region of southern Italy. 

"The group's love of their land is a common theme and gives them a purpose in life. Most of them are still working in their homes and on the land. They think, 'This is my life and I'm not going to give it up,'" said Anna Scelzo, first author of the study with the Department of Mental Health and Substance Abuse in Chiavarese, Italy. Interview responses also suggested that the participants had considerable self-confidence and decision-making skills. "This paradox of aging supports the notion that well-being and wisdom increase with aging even though physical health is failing," said Jeste, also the Estelle and Edgar Levi Chair in Aging and director of the Sam and Rose Stein Institute for Research on Aging at UC San Diego.

"We also found that this group tended to be domineering, stubborn and needed a sense of control, which can be a desirable trait as they are true to their convictions and care less about what others think," said Scelzo. "This tendency to control the environment suggests notable grit that is balanced by a need to adapt to changing circumstances." [Original study.

Rural village in the region of Cilento,  Italy. Credit: Wikipedia.

Published on Leave a comment on Slight Increased Risk of Breast Cancer From Low Dose Hormonal Birth Control

 The findings of a large study from Denmark were a disappointment for those hoping that women taking or using low dose hormonal birth control (pills, IUD) would not show an increase in breast cancer (like the old higher dose birth control pills). This study found a small increase in the risk of breast cancer with the use of modern birth control pills and with a progestin-only intrauterine device. They pointed out that the biggest risk was in those using hormonal methods for over 10 years and in their 40s (most of the breast cancer cases occurred in this group of women). The risk goes up the longer one uses hormonal contraception.

Due to smaller numbers of women using a birth control patch, vaginal ring, and implants - they were unable to say one way or another if these also are linked to a higher incidence of breast cancer. But the sense from the researchers is that all hormonal contraception has a slight increase in risk of breast cancer. How big an increase in risk? There is a 20% increased risk overall, but the actual numbers are fairly small - 13 per 100,000 women or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year. From Medical Xpress:

Small risk of breast cancer seen with hormone contraceptives

Modern birth control pills that are lower in estrogen have fewer side effects than past oral contraceptives. But a large Danish study suggests that, like older pills, they still modestly raise the risk of breast cancer, especially with long-term use. Researchers found a similar breast cancer risk with the progestin-only intrauterine device, and they couldn't rule out a risk for other hormonal contraceptives like the patch and the implant.

But the overall increased risk was small, amounting to one extra case of breast cancer among 7,700 women using such contraceptives per year. Experts who reviewed the research say women should balance the news against known benefits of the pill - including lowering the risk of other cancers.

Researchers analyzed health records of 1.8 million women, ages 15 to 49, in Denmark where a national health care system allows linking up large databases of prescription histories, cancer diagnoses and other information. Results were published Wednesday in the New England Journal of Medicine. Novo Nordisk Foundation funded the research, but played no role in designing the study.

Current and recent use of hormonal contraceptives was associated with a 20 percent increased risk of breast cancer. Risk increased with longer use, from a 9 percent increase in risk with less than a year of contraceptive use to a 38 percent increase after more than 10 years of use. Digging further, the researchers found no differences among types of birth control pills. Because of fewer users, the results for the patch, vaginal ring, implant and progestin shot were less clear, but the analysis didn't rule out an increased breast cancer risk for those methods. [Original study.]

Published on Leave a comment on Exercise Alters Gut Microbes In A Beneficial Way

Two studies (one in mice and one in humans) by researchers at the University of Illinois found that no matter what your diet - exercise changes the gut bacteria in a beneficial way. And when you go back to a sedentary lifestyle, your gut microbes change again and beneficial microbes such as short chain fatty acids (SCFAs), especially butyrates, decline. The effect was more pronounced in lean sedentary adults (as compared to obese sedentary adults).

Beneficial microbes that increased with exercise in humans were species of Faecalibacterium, Roseburia, Lachnospira, Lachnospiraceae, and Clostridiales. Faecalibacterium prausnitzii has been discussed in earlier posts as a beneficial keystone species in the gut (here, here, and here).

What kind of exercises did they do? They did three supervised 30 to 60 minute moderate to vigorous intensity aerobic/endurance exercise sessions per week for 6 weeks, and they could use a cycle ergometer (stationary bicycle) or treadmill each session.

Besides beneficial microbial changes, 6 weeks of exercising resulted in improved body composition (total lean body mass, decreased body fat, increased bone mineral density), and an improvement in cardiorespiratory fitness. These changes reversed in everyone when they went back to 6 weeks of a sedentary lifestyle.

Bottom line: get out and move, move, move. Your gut microbes and your body will thank you.

From Science Daily: Exercise changes gut microbial composition independent of diet, team reports

Two studies -- one in mice and the other in human subjects -- offer the first definitive evidence that exercise alone can change the composition of microbes in the gut. The studies were designed to isolate exercise-induced changes from other factors -- such as diet or antibiotic use -- that might alter the intestinal microbiota.

In the first study, scientists transplanted fecal material from exercised and sedentary mice into the colons of sedentary germ-free mice, which had been raised in a sterile facility and had no microbiota of their own. In the second study, the team tracked changes in the composition of gut microbiota in human participants as they transitioned from a sedentary lifestyle to a more active one -- and back again.

Recipients of the exercised mouse microbiota also had a higher proportion of microbes that produce butyrate, a short-chain fatty acid that promotes healthy intestinal cells, reduces inflammation and generates energy for the host. They also appeared to be more resistant to experimental ulcerative colitis, an inflammatory bowel disease.

In the human study, the team recruited 18 lean and 14 obese sedentary adults, sampled their gut microbiomes, and started them on an exercise program during which they performed supervised cardiovascular exercise for 30-60 minutes three times a week for six weeks. The researchers sampled participants' gut microbiomes again at the end of the exercise program and after another six weeks of sedentary behavior. Participants maintained their usual diets throughout the course of the study. Fecal concentrations of SCFAs, in particular butyrate, went up in the human gut as a result of exercise. These levels declined again after the participants reverted to a sedentary lifestyle.

The most dramatic increases were seen in lean participants, who had significantly lower levels of SCFA-producing microbes in their guts to begin with. Obese participants saw only modest increases in the proportion of SCFA-producing microbes. The ratios of different microbes in the gut also differed between lean and obese participants at every stage of the study, the researchers said. "The bottom line is that there are clear differences in how the microbiome of somebody who is obese versus somebody who is lean responds to exercise," Woods said. " [Original study in humans.]

Published on Leave a comment on Blood Pressure Declines For More Than A Decade Before Death

This is interesting, that blood pressure naturally starts lowering in the 14 to 18 years prior to death in people 60 years or older - whether they are healthy, have hypertension, have heart disease, take hypertension medicines or not.

The researchers analyzed 20 years of medical data for patients in the United Kingdom, and while everyone's blood pressure dropped for more than a decade before death, the decreases were "steepest in patients with hypertension, dementia, heart failure, and late-life weight loss".

From Science Daily: Blood pressure declines 14 to 18 years before death

Blood pressure in the elderly gradually begins to decrease about 14 or so years before death, according to a new study published today in the Journal of the American Medical Association Internal Medicine. Researchers from UConn Health and the University of Exeter Medical School in the U.K. looked at the electronic medical records of 46,634 British citizens who had died at age 60 or older. The large sample size included people who were healthy as well as those who had conditions such as heart disease or dementia.

They found blood pressure declines were steepest in patients with dementia, heart failure, late-in-life weight loss, and those who had high blood pressure to begin with. But long-term declines also occurred without the presence of any of these diagnoses.

Doctors have long known that in the average person, blood pressure rises from childhood to middle age. .... Some studies have indicated that blood pressure might drop in older patients and treatment for hypertension has been hypothesized as explaining late-life lower blood pressures. But this study found blood pressure declines were also present in those without hypertension diagnoses or anti-hypertension medication prescriptions. Further, the evidence was clear that the declines were not due simply to the early deaths of people with high blood pressure. [Original study.]