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Author: Sima

Published on Leave a comment on Treat Localized Prostate Cancer Or Not?

This is similar to what Dr. Gilbert Welch and others have been saying for a while - that studies show much cancer screening leads to overdiagnosis and overtreatment with no real differences in rates of mortality (death). Which was the whole point of cancer screening - to catch cancers early and so reduce rates of death. (For more on this topic see here, here, here, and here.) There are harms from overtreatment (unnecessary treatment), and with prostate cancer treatment there can be adverse effects on sexual (erectile dysfunction) , urinary, or bowel function, and sometimes even death from surgery. Remember that many prostate cancers are "indolent" or very slow growing, and may remain asymptomatic throughout the man's lifetime. Currently the U.S. Preventive Services Task Force (USPSTF) recommends against prostate-specific antigen (PSA)-based screening for prostate cancer for these reasons.

This study in the New England Journal of Medicine reported on men diagnosed with prostate cancer, with the men then assigned to either monitoring or treatment (surgery or radiation), and then followed for 10 years. Much to the researchers' surprise, the survival rates from prostate cancer were equally high in all the groups - 99%. Now, as the researchers themselves point out - the groups of men need to be followed for more years. Will there be differences after 15 or 20 years? Also, if there is prostate cancer progression in the monitored group (and more men did have disease progression in this group after 10 years, even though the numbers were low), can it still be treated just as successfully? More studies are needed. Note that there was cancer progression among some men even in both treatment groups.

Other important prostate cancer studies are also needed. Are there differences among those men for whom cancer progresses and for those that it doesn't? Does intense exercise make a difference (as some think)? Dietary differences, such as a plant based diet? Body fat or weight? From Science Xpress: Treat or monitor early prostate cancer? 10-yr survival same

Men with early prostate cancer who choose to closely monitor their disease are just as likely to survive at least 10 years as those who have surgery or radiation, finds a major study that directly tested and compared these options. Survival from prostate cancer was so high—99 percent, regardless of which approach men had—that the results call into question not only what treatment is best but also whether any treatment at all is needed for early-stage cases. And that in turn adds to concern about screening with PSA blood tests, because screening is worthwhile only if finding cancer earlier saves lives.

The study involved more than 82,000 men in the United Kingdom, aged 50 to 69, who had tests for PSA, or prostate specific antigen. High levels can signal prostate cancer but also may signal more harmless conditions, including natural enlargement that occurs with age. Researchers focused on the men diagnosed with early prostate cancer, where the disease is small and confined to the prostate. Of those men, 1,643 agreed to be randomly assigned to get surgery, radiation or active monitoring. That involves blood tests every three to six months, counseling, and consideration of treatment only if signs suggested worsening disease.

A decade later, researchers found no difference among the groups in rates of death from prostate cancer or other causes. More men being monitored saw their cancers worsen—112 versus 46 given surgery and 46 given radiation. But radiation and surgery brought more side effects, especially urinary, bowel or sexual problems....PSA testing remains popular in the U.S. even after a government task force recommended against it, saying it does more harm than good by leading to false alarms and overtreatment of many cancers that would never threaten a man's life. In Europe, prostate cancer screening is far less common.

From the original study in the The New England Journal of Medicine: 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer

The comparative effectiveness of treatments for prostate cancer that is detected by prostate-specific antigen (PSA) testing remains uncertain.  In the United States alone, an estimated 180,890 cases will be diagnosed in 2016, and 26,120 men will die from the disease.1 The widespread use of PSA testing has resulted in a dramatic increase in the diagnosis and treatment of prostate cancer, but many men do not benefit from intervention because the disease is either indolent or disseminated at diagnosis. Prostate cancer often progresses slowly, and many men die of competing causes. In addition, interventions for prostate cancer can have adverse effects on sexual, urinary, or bowel function. Two treatment trials have evaluated the effectiveness of treatment, but they did not compare the most common contemporary methods: surgery, radiotherapy, and monitoring or surveillance

We compared active monitoring, radical prostatectomy, and external-beam radiotherapy for the treatment of clinically localized prostate cancer. Between 1999 and 2009, a total of 82,429 men 50 to 69 years of age received a PSA test; 2664 received a diagnosis of localized prostate cancer, and 1643 agreed to undergo randomization to active monitoring (545 men), surgery (553), or radiotherapy (545). The primary outcome was prostate-cancer mortality at a median of 10 years of follow-up. Secondary outcomes included the rates of disease progression, metastases, and all-cause deaths.

There were 17 prostate-cancer–specific deaths overall: 8 in the active-monitoring group (1.5 deaths per 1000 person-years; 95% confidence interval [CI], 0.7 to 3.0), 5 in the surgery group (0.9 per 1000 person-years; 95% CI, 0.4 to 2.2), and 4 in the radiotherapy group (0.7 per 1000 person-years; 95% CI, 0.3 to 2.0); the difference among the groups was not significant (P=0.48 for the overall comparison). In addition, no significant difference was seen among the groups in the number of deaths from any cause (169 deaths overall; P=0.87 for the comparison among the three groups). Metastases developed in more men in the active-monitoring group (33 men; 6.3 events per 1000 person-years; 95% CI, 4.5 to 8.8) than in the surgery group (13 men; 2.4 per 1000 person-years; 95% CI, 1.4 to 4.2) or the radiotherapy group (16 men; 3.0 per 1000 person-years....). Higher rates of disease progression were seen in the active-monitoring group (112 men; 22.9 events per 1000 person-years; 95% CI, 19.0 to 27.5) than in the surgery group (46 men; 8.9 events per 1000 person-years; 95% CI, 6.7 to 11.9) or the radiotherapy group (46 men; 9.0 events per 1000 person-years....).

At a median of 10 years, prostate-cancer–specific mortality was low irrespective of the treatment assigned, with no significant difference among treatments. Surgery and radiotherapy were associated with lower incidences of disease progression and metastases than was active monitoring.

Published on Leave a comment on Reading Books Linked To Living Longer

 Image result for books wikipedia There are some things we can do that are linked to living longer, such as not smoking and exercising regularly, but could reading books also have such an effect? A study published in the journal Social Science and Medicine concludes that those who regularly read books add several years to their lives. They found this effect in both men and women, found that reading books are "protective regardless of gender, wealth, education", but the effect holds only for books and not magazines and newspapers. Since surveys show that 87% of book readers read fiction, then it is likely that most of the book readers were reading fiction.

In the long-term (12 years) study of 3,635 people, the researchers found that those that read books for more than 3.5 hours per week lived on average two years longer than non-readers, and that there was a dose-response effect (the more one reads, the better). This appeared to be linked to cognitive enhancement rather than any other associated factor, such as age, sex, education, race, health, wealth, etc. The research team from the Yale University School of Public Health divided their subjects into three groups: those who didn’t read at all, those who read for 3.5 hours per week or less, and those who read for more than 3.5 hours per week. They found that the occasional readers were 17 percent less likely to die during the follow-up period than those who did not. This beneficial effect of reading was only linked to books, and not other forms of reading material such as magazines or newspapers. From the journal Social Science and Medicine:

A chapter a day: Association of book reading with longevity

This study examined whether those who read books have a survival advantage over those who do not read books and over those who read other types of materials, and if so, whether cognition mediates this book reading effect. The cohort consisted of 3635 participants in the nationally representative Health and Retirement Study who provided information about their reading patterns at baseline.....based on survival information up to 12 years after baseline. A dose-response survival advantage was found for book reading by tertile.....Book reading contributed to a survival advantage that was significantly greater than that observed for reading newspapers or magazines. Compared to non-book readers, book readers had a 23-month survival advantage at the point of 80% survival in the unadjusted model. A survival advantage persisted after adjustment for all covariates (HR = .80, p < .01), indicating book readers experienced a 20% reduction in risk of mortality over the 12 years of follow up compared to non-book readers. Cognition mediated the book reading-survival advantage. These findings suggest that the benefits of reading books include a longer life in which to read them.

While most sedentary behaviors are well-established risk factors for mortality in older individuals (Wullems et al., 2016; de Rezenade et al., 2014, Katzmaryk & Lee, 2012; Muennig, Rosen, & Johnson, 2013), previous studies of a behavior which is often sedentary, reading, have had mixed outcomes....We speculated that books engage readers’ minds more than newspapers and magazines, leading to cognitive benefits that drive the effect of reading on longevity. 

Reading books tends to involve two cognitive processes that could create a survival advantage. First, it promotes "deep reading,” which is a slow, immersive process; this cognitive engagement occurs as the reader draws connections to other parts of the material, finds applications to the outside world, and asks questions about the content presented (Wolf, Barzillai, & Dunne, 2009). Cognitive engagement may explain why vocabulary, reasoning, concentration, and critical thinking skills are improved by exposure to books (Stanovich, West, & Harrison, 1995; Stanovich & Cunningham, 1998; Wolf, Barzillai, & Dunne, 2009). Second, books can promote empathy, social perception, and emotional intelligence, which are cognitive processes that can lead to greater survival (Bassuk, Wypij, & Berkmann, 2000; Djikic, Oatley, & Moldoveanu 2013; Kidd & Castano 2013; Shipley, Der, Taylor, & Deary 2008; Olsen, Olsen, Gunner-Svensson, & Waldstrom, 1991).

The final sample consisted of 3635 individuals that were followed over 34,496 person years, with 27.4% of the sample dying during an average 9.49 years of follow-up. Consistent with the older population, the sample was predominantly (62%) female.....The average time spent reading per week was 3.92 hours for books and 6.10 hours for periodicals. The two types of reading were not strongly correlated, and 38% of the sample (n=1390) read only books or only periodicals; this allowed them to be treated as separate constructs.....Cognitive engagement was assessed with total cognitive score (available in the supplemental Imputation of Cognitive Function Measures) which is a summary variable based on 8 items, including immediate recall, delayed recall, serial 7s, backwards count from 20, object naming, President naming, Vice President naming, and date naming.

A 20% reduction in mortality was observed for those who read books, compared to those who did not read books. Further, our analyses demonstrated that any level of book reading gave a significantly stronger survival advantage than reading periodicals.....The mediation analyses showed for the first time that the survival advantage was due to the effect that book reading had on cognition....This finding suggests that reading books provide a survival advantage due to the immersive nature that helps maintain cognitive status.

Published on Leave a comment on Laser Pointers Are Not Toys and Can Cause Vision Loss

It has long been known that laser pointers can be damaging to the eyes, but apparently this is not widely known. Injuries to the eyes (retinal injuries) causing irreversible vision loss are rapidly increasing from them, especially among children. Injuries to the eye happen when a person stares directly into the laser pointer, or even into the reflection in a mirror. This can inadvertently happen among children, for example when playing games such as laser tag.

A laser pointer is a small handheld device that contains a small diode laser that emits a very narrow beam of light, used to highlight something of interest.during presentations. They are also inappropriately used as toys for some children. The researchers point out that "green laser pointers are becoming increasingly more popular and abundantly available, which is concerning because experiments reveal that green laser pointers (490–575 nm) are more harmful to the retina compared with red laser pointers (630–750 nm)". From Medscape:

Laser Pointers Can Cause Irreversible Vision Loss for Kids

Used incorrectly, laser pointers can damage the retina of the eye and may cause some irreversible vision loss, according to researchers who treated four boys for these injuries. Doctors, teachers and parents should be aware that this can happen, and limit children's use of laser pointers, the authors write.

The authors report on two 12-year-olds, one nine-year-old and one 16-year-old who came to a medical center with central vision loss and "blind spots" within hours to days after looking into or playing with a green or red laser pointer. In one case, the boy looked at the reflection of a laser pointer in a mirror. Two others simply pointed the lasers at themselves, and the fourth was engaged in a "laser war" with a friend.

The researchers report in Pediatrics September 1st that three of the boys had potentially irreversible, although relatively mild, vision loss. One boy's vision continued to worsen two weeks after the injury and eventually decreased to 20/40 best corrected visual acuity in both eyes, which is at or close to the limit for obtaining a driver's license in most U.S. states.

He advises parents to be careful about where they buy laser pointers, as some retailers may not list the power rating or may list it incorrectly, and to limit use for kids under 14. Most consumer laser pointers fall under class II or class IIIA level of safety according to the American National Standard Institute, with a power output of five milliwatts or less. But class 3B or class 4 level lasers may emit up to 500 milliwatts or more and these lasers may cause immediate eye hazard when viewed directly, Almeida and his coauthors write.

Retinal tissue in the back of the eye leads to the brain, and it has no ability to regenerate after tissue loss, Almeida said.

Published on Leave a comment on Poop Pills Work!

The latest development in treating stubborn cases of Clostridium difficile infections (CDI) are "poop pills" - pills that patients can easily swallow rather than having to go through a fecal microbiota transplant (FMT). The "poop pills" are filled with blenderized fecal matter from healthy donors, are much easier for patients to swallow, and they successfully treat C. difficile at almost the same rate as fecal microbiota transplants - about 91% after 1 or 2 treatments for the pills, and 93 to 96% for FMT. This is an amazing success rate for an infection that debilitates people, is resistant to antibiotics in many cases, and even kills people.

Interestingly, these "poop pills" or "Capsule FMT" containing an entire microbiome (bacteria, viruses, fungi, etc) had fantastic results, as compared to a probiotic for the treatment of C. difficile tested by microbiome therapeutics company Seres Therapeutics Inc. In July 2016 Seres announced very disappointing results (no better than a placebo) with its product known as SER-109, a mix of various strains of bacteria.

So why did the Seres probiotic not work in clinical trails? The answer seems to be that the human gut (and so also human fecal matter) contains an entire community of microbes - hundreds of species of bacteria, as well as fungi, viruses, and archaea, but the Seres probiotic was just a mixture of some types of bacteria. This shows how little we know right now. (NOTE: For those interested, the "poop pills" or Capsule FMT is now offered as standard care for recurrent CDI at Massachusetts General Hospital.) From BioMedCentral:

Oral, frozen fecal microbiota transplant (FMT) capsules for recurrent Clostridium difficile infection

Fecal microbiota transplantation (FMT) has been shown to be safe and effective in treating refractory or relapsing C. difficile infection (CDI), but its use has been limited by practical barriers. We recently reported a small preliminary feasibility study using orally administered frozen fecal capsules. Following these early results, we now report our clinical experience in a large cohort with structured follow-up. We prospectively followed a cohort of patients with recurrent or refractory CDI who were treated with frozen, encapsulated FMT at our institution. The primary endpoint was defined as clinical resolution whilst off antibiotics for CDI at 8 weeks after last capsule ingestion. Safety was defined as any FMT-related adverse event grade 2 or above.

Overall, 180 patients aged 7–95 years with a minimal follow-up of 8 weeks were included in the analysis. CDI resolved in 82 % of patients after a single treatment, rising to a 91 % cure rate with two treatments. Three adverse events Grade 2 or above, deemed related or possibly related to FMT, were observed. We confirm the effectiveness and safety of oral administration of frozen encapsulated fecal material, prepared from unrelated donors, in treating recurrent CDI. Randomized studies and FMT registries are still needed to ascertain long-term safety.

The epidemiology of Clostridium difficile infection (CDI) is evolving. Rates of infection are increasing and response to standard antimicrobial treatment with metronidazole or vancomycin may be suboptimal [1, 2].....Fecal microbiota transplant (FMT) has been shown to be safe and effective in treating refractory or relapsing CDI [4, 5, 6, 7, 8], but its use has been limited by practical barriers. Among other concerns, the administration of FMT by colonoscope or naso-gastric/duodenal tube exposes the patient to some risk and discomfort. We recently reported a preliminary feasibility study using orally administered frozen fecal capsules, prepared from unrelated donors, to treat 20 patients with recurrent CDI [9]. Following these encouraging results, we have continued treating patients with FMT capsules. We report our clinical experience in a large cohort with structured follow-up.

Donated fecal matter was blenderized, sieved, centrifuged, and suspended in concentrated form in sterile saline with 10 % glycerol. The suspension was double-encapsulated in hypromellose capsules (Capsugel, Cambridge, MA) and stored at –80 °C for up to 6 months pending use. Processing was done entirely under ambient air. FMT recipients discontinued any anti-CDI treatment for 24–48 hours prior to FMT, and were given 15 capsules on each of two consecutive days with water or apple sauce. The 30 capsules contained sieved, concentrated material derived from a mean of 48 g of fecal matter.

Of the 180 patients reaching 8 weeks, 147 were cured of CDI after the first administration of fecal capsules (82 %). Twenty six individuals relapsed within 8 weeks and were re-treated, with 17 responding, resulting in an overall cure rate of 91 % with one or two treatments. Six individuals declined re-treatment (our standard procedure in these cases is to offer long-term suppressive oral vancomycin treatment). Three patients were cured after a third administration, but were considered “non-responders” as per protocol definition. One patient received three treatments, relapsed, and was advised to continue suppressive vancomycin.

Published on Leave a comment on The Development of Antibiotic Resistant Bacteria

Here is an amazing short video for those interested in seeing how bacteria mutate and grow when exposed to antibiotics - and evolving to become superbugs. Researchers filmed an experiment that created bacteria a thousand times more drug-resistant than their ancestors. In the time-lapse video, a white bacterial colony (E.coli bacteria) creeps across an enormous black petri dish plated with vertical bands of successively higher doses of antibacterial drugs (antibiotics).

How they did it: The researchers imaged the E. coli bacteria every 10 minutes for 10 days as the microbes expanded across the plate. You can see that the bacteria paused briefly at the boundaries of increasingly stronger antibiotic concentrations until a mutant bacteria struck out into the stronger antibiotic territory. By challenging the bacteria with differing doses of antibiotic, the team demonstrated that E. coli evolve higher resistance more quickly if they first encounter an intermediate, rather than a high, concentration of antibiotic. It's a beautiful, yet horrifying video. NOTE: the bacteria grows on agar, which is a thick, clear substance that comes from seaweed and is used for growing bacteria in scientific research. From Harvard Medical School, on YOUTUBE:

From NPR:  WATCH: Bacteria Invade Antibiotics And Transform Into Superbugs

In the time-lapse video, a white bacterial colony creeps across an enormous black petri dish plated with vertical bands of successively higher doses of antibiotic. The colony pauses when it hits the first band of antibiotic, creating a stark border between the white colony and the black petri dish. Then the bacteria start to edge their way into the toxic soup. More dots appear and they start growing, racing to the next, stronger band of antibiotic. The bacteria are evolving. After almost two weeks of real time have passed, they've become resistant to the strongest completely taken over the kitchen-table-sized petri dish.

We know dangerous bacteria are getting stronger all the time and that it's our fault because of our excessive and indiscriminate use of antibiotics. Each year, 23,000 people in the U.S. die as a result of superbug infections. But we typically don't get to see superbugs created.... Their video and report were published Thursday in the journal Science. 

Published on Leave a comment on Avoid Lavender and Tea Tree Oils In Personal Care Products?

Over the years I have read about some oils, especially lavender and tea tree oils,  as having hormone altering (endocrine disrupting) effects when used over prolonged periods of time or when someone is "chronically exposed". Especially worrisome was the possible estrogenic effects of lavender oils in shampoos, lotions, and soaps on developing children - especially boys (prolonged use leading to the development of breasts in some boys!). I just read a recently published journal study (with very interesting comments at the end), and an article in WebMD about this same topic. The condition of early breast development is called prepubertal gynecomastia in boys and thelarche in girls.

As you can imagine, the industry (Australian Tea Tree Industry Association and Research Institute for Fragrance Materials Inc) calls such research  "poor science". Of course industry sponsored "research" never ever finds any problems (because any "problems" would impact the big $$ from the sale of those products). In fact, I would be skeptical of any industry sponsored research in this area - it is not truly independent, unbiased research if they "have to" and "want to" find no problems. So when you do read industry research, also read the rebuttals by independent scientists and doctors.

Bottom line: No matter the age, avoid prolonged use of lavender and tea tree oil in personal care products, including "aromatherapy" -  especially important for children and pregnant women. The good news is that the development of breasts in young children is reversible when use of the product is stopped. But better to avoid such products (including Agua de Violetas) on children in the first place. Instead use unscented personal care products.

From WebMD:  Are Tea Tree and Lavender Oils Safe for Kids?

Tea tree and lavender essential oils are popular ingredients in personal care and household products, including many aimed at children. But can the ingredients, often promoted as “natural” alternatives, trigger abnormal breast growth in boys and girls? A few small studies suggest that frequently using lotions, shampoos, styling gels, and even a certain cologne containing lavender and tea tree oils may cause breast growth in boys, also known as gynecomastia, along with breast growth in girls as young as 4 or 5. 

Other studies have not reached the same conclusions, and the cases appear to be rare. In addition, scientific research into most natural products is scant. The FDA doesn’t oversee essential oils unless they are intended for use in a drug, making it challenging to know how safe and effective these products are....Lavender and tea tree oils are among the most commonly used essential oils used. Although research is inconclusive, lavender is often used for aromatherapy and calming lotions, while tea tree oil is promoted for acne, nail fungus, and other skin conditions. 

...continue reading "Avoid Lavender and Tea Tree Oils In Personal Care Products?"

Published on Leave a comment on Paradigm Shift In Thinking About Urinary Tract Infections

This article by Dr. Thomas E. Finucane lays out nicely a paradigm shift in how to view uncomplicated urinary tract infections (UTIs) - as a case of dysbiosis (microbial community out of whack), and that antibiotics to kill bacteria are generally not needed or helpful. (He doesn't mention it, but the next step in his argument should be that probiotic or beneficial bacteria or other microbes may improve the microbial community and symptoms.) A main point of the article is that we now know the urinary tract is not sterile - instead diverse microbiota live there (the microbial community is the microbiome) including bacteria and viruses (the virome), and that these stable microbial communities are generally beneficial. Standard cultures do not pick up all the microbes living in the urinary tract.

He points out that: UTI symptoms are usually self-limited, of brief duration and only slightly shortened by antibiotic treatment; that cystitis rarely progresses to pyelonephritis (which does need antibiotic treatment); and that randomized trials show no reduction in the risk of progression to pyelonephritis with antibiotic treatment. He stresses the "generally benign (other than symptoms) nature of “symptomatic UTI” is suggested by the billions of persons around the world and over the years who have suffered “UTI” without access to antibiotics and have recovered fully". And that "urinary tract dysbiosis" may be a better description of what a woman is experiencing.

However, I would like to add that to a person experiencing an UTI, the pain does not at all feel "benign". So look at the posts on UTIs and treatments and perhaps try something like D- mannose  or cranberry supplements, or both. From The American Journal of Medicine:

“Urinary tract infection” and the microbiome

The current paradigm for managing uncomplicated “urinary tract infection” (“UTI”) is deeply flawed. “UTI” is ambiguously defined and, coupled with a belief that “bacteria are not normal inhabitants of the urinary tract, the diagnosis often leads to unnecessary, harmful antibiotic treatment. Although bacteriuria identified by standard clinical cultures (which we will call standard bacteriuria) is central to most definitions, more sensitive diagnostic tests now demonstrate that “urine is not sterile”2 and that standard bacteriuria represents a fraction of the diverse microbiota hosted by the urinary tract. Knowledge of this complex, generally beneficial microbiome deeply undermines the current paradigm, which relies on the findings of standard culture. By acknowledging this microbiome a successor paradigm will generate new questions about relationships among host, microbiome and antibiotic use and will almost surely show additional serious harms from antibiotic overtreatment.

This discussion concerns medically stable, non-pregnant adults with normal urinary tract structure and function. The role of antibiotics in patients with abnormalities of anatomy or physiology, such as spinal cord injury, urinary obstruction, or catheters, will require careful investigation. New insight into pyelonephritis and bacteremic bacteriuria is likely to develop.

The ambiguous definition of “UTI” seems to promote antibiotic overuse. In one common usage, “urinary tract infection is defined as microbial infiltration of the normally sterile urinary tract.” With this definition, asymptomatic bacteriuria is a “UTI” and is often treated, even in patient groups where strong evidence shows lack of benefit.4 A second common definition, “significant bacteriuria in a patient with symptoms or signs attributable to the urinary tract and no alternate source” seems more restrictive but does not define what symptoms or signs may be attributed to the urinary tract. This ambiguity creates opportunities for overtreatment....Antibiotic treatment of “UTI” often follows even though no data have shown these changes respond to treatment.

Canonically, “all symptomatic UTI should be treated” but actual benefit is limited. Hooton emphasizes that in acute uncomplicated cystitis “the primary goal of treatment is to ameliorate symptoms.” Foxman summarizes that symptoms are usually self-limited, of brief duration and only slightly shortened by antibiotic treatment; that cystitis rarely progresses to pyelonephritis; and that randomized trials show no reduction in the risk of progression to pyelonephritis with antibiotic treatment.7 The generally benign (other than symptoms) nature of “symptomatic UTI” is suggested by the billions of persons around the world and over the eons who have suffered “UTI” without access to antibiotics and have recovered fully.

With its various meanings, convenient diagnosis, long tradition, suggestive link to treatment and uncritical acceptance by clinicians, patients, families and insurers, “UTI” remains heavily embedded in practice, “one of the most common bacterial infections worldwide”. The paradigm provides tidy management for a patient with “UTI” who expects antibiotics. Further, the current paradigm does account for several findings. Standard bacteriuria is associated with pyuria, fever and dysuria, for example, and these often improve with treatment, as do a wide variety of findings seemingly unconnected with the urinary tract. Antibiotic treatment improves outcomes for asymptomatic pregnant women who have standard bacteriuria. Pyelonephritis and bacteremic bacteriuria probably arise in the urinary tract and do require antibiotic treatment.

To diagnose “UTI” and determine antibiotic sensitivity based on results of standard cultures, however, is to rely on familiar, accessible data and to ignore the dozens of bacterial species, as well as intracellular bacterial colonies and urinary virome known to reside in the urinary tract. Current discussions of symptomatic or asymptomatic bacteriuria or sterile urine are similarly problematic. To attribute delirium to standard bacteriuria seems unjustifiable, knowing that most or all people with or without delirium have bacteriuria. The current paradigm is defensible only if all pathogenic organisms are identified with standard cultures and all organisms more difficult to identify can be safely ignored.

We propose instead that urinary symptoms, bacteremia, pyelonephritis, and other recognizable disturbances of the urinary tract are the dysbiotic tip of a much larger iceberg of complex host-microbe interactions that are occurring out of sight of standard cultures. As expected in the era of the microbiome, stable bacterial communities are generally beneficial. For example, compared with the instillation of sterile saline, “bladder colonization with (the nonpathogenic) E. coli HU2117 safely reduces the risk of symptomatic urinary tract infection in patients with spinal cord injury”.8 Of 699 young women with asymptomatic bacteriuria, half of whom were randomized to receive no antibiotic treatment, “treatment was associated with a higher rate of symptomatic UTI… (thus) asymptomatic bacteriuria … may play a protective role in preventing symptomatic recurrence” during 12-month follow-up.9

Costello and colleagues outline a broader paradigm shift in the general approach to infection; “transitioning clinical practice from the Body-as-Battleground to the Human-as-Habitat perspective will require rethinking how one manages the human body.”10 To help in this transition, mindful language will be important. We suggest that authors use “UTI” only within quotation marks and that clinicians use the bimanual “air quotes” gesture in discussions. This small, repetitive annotation is intended to disrupt the term’s complacent usage and encourage rethinking of how one manages bacteriuria. The term “urinary tract dysbiosis” may be useful for otherwise well patients with urinary tract symptoms.

“UTI” is an ill-defined, glibly overdiagnosed and overtreated “infection”. Current management ignores modern science. The associated antibiotic overuse causes serious harm to patient safety and to public health. Instead of the current-paradigm question, “Does this patient have a UTI?” the successor-paradigm question will be, “Does evidence show that antibiotic treatment is likely to benefit this patient?” Shifting the paradigm is an urgent matter.

Published on Leave a comment on Vitamin D Levels and Mental Decline In Older Adults

A new study conducted in China found an association between low vitamin D levels and future cognitive decline in older adults. The lower the vitamin D levels at the initial screening (the baseline), the more people with cognitive decline at a 2 year follow-up. There were were no gender differences. (Another study with similar results.) Vitamin D is produced naturally in the skin when exposed to sunlight, and also found in smaller amounts in food such as fish (e.g. salmon) and eggs. Vitamin D helps maintain healthy bones and muscles, but it also plays a key part in brain function and is viewed as neuroprotective. Low levels are associated with greater risk of cardiovascular and neurodegenerative diseases.

The 1,202 participants (60 years or older) in China had their baseline vitamin D levels measured at the start of the study, and their cognitive abilities assessed over two years. What I found interesting in this study was that the vitamin D levels in the people was in general pretty low - this was without any supplementation, thus from sunlight. The researchers specified vitamin D levels (25-Cholecalciferol) in nmol/l, but in the United States values are generally specified in ng/ml. In the study the median level of vitamin D levels in the lowest quartile converted to ng/ml was 10.0 ng/ml, and in the highest quartile the median level was 26.4 ng/ml. With those low numbers, all 4 groups in the United States would be advised to supplement daily with vitamin D (specifically vitamin D3). From Journals of Gerontology: Medical Sciences:

Vitamin D Levels and the Risk of Cognitive Decline in Chinese Elderly People: the Chinese Longitudinal Healthy Longevity Survey

Vitamin D has a neuroprotective function, potentially important for the prevention of cognitive decline. Prospective studies from Western countries support an association between lower vitamin D level and future cognitive decline in elderly people.

This community-based cohort study of elderly people in China follows 1,202 cognitively intact adults aged ≥60 years for a mean duration of 2 years. Plasma vitamin D level was measured at the baseline. Cognitive state of participants was assessed using the Mini-Mental State Examination (MMSE). Cognitive impairment was defined as an MMSE score <18. Cognitive decline was defined as ≥3 points decline from baseline....Participants with low vitamin D level had an increased risk of cognitive decline. This first follow-up study of elderly people, including the oldest-old, in Asia shows that low vitamin D levels were associated with increased risk of subsequent cognitive decline and impairment.

Vitamin D is a secosteroid hormone necessary for maintaining good musculoskeletal health; its deficiency is associated with increased risks of cardiovascular and neurodegenerative diseases. Vitamin D is primarily synthesized in the skin upon exposure to sunlight; smaller amounts are obtained through dietary intake. More recently, enzymes responsible for the synthesis of its active form have been found to be distributed throughout the human brain.... This growing body of evidence suggests that vitamin D has a neuroprotective function that is potentially important for the prevention of cognitive decline. Although the importance of vitamin D cannot be disregarded, there is still no consensus on its optimal level. This is especially pertinent in the elderly people, the oldest-old in particular, as cutaneous synthesis of vitamin D decreases with age. Moreover, their impaired mobility and limited outdoor activities can further exacerbate vitamin D deficiency.

Cross-sectional studies have generally found a positive association between vitamin D status and cognitive performance in older adults. Recent prospective studies from United States and Europe support an association between diminished vitamin D status and future cognitive decline. Since cutaneous synthesis is the main source of vitamin D, there exists great variability in vitamin D levels across populations due to differences in latitude, seasons, and race/ethnicity, such as level of skin pigmentation.

Our findings were consistent with previous cohort studies showing that vitamin D status predicts cognitive decline....A notable observation in the present study is that the association of vitamin D status and cognitive decline were similar in both oldest-old and less elderly people. In this study, there was a clear association between lower 25(OH)D3 level and cognitive impairment in subjects aged ≥80....An additional difference from previous studies is that the current study indicates that the association between vitamin D and cognitive impairment is not gender specific.

The observation of temporal association between 25(OH)D3 levels and subsequent cognitive function supports the notion that vitamin D has a clinically important neuroprotective effect. A wide variety of mechanisms for this effect has been proposed and is supported by animal studies. Vitamin D has been found to modulate neuronal calcium homeostasis, cerebral process of detoxification, immunomodulation, and beta-amyloid clearance.....Further, it was unlikely that vitamin D supplementation would explain the association in this study, as 87% of the participants reported no use of vitamin supplements....In conclusion, our longitudinal study indicates that low 25(OH) D3 levels are associated with subsequent cognitive decline and cognitive impairment. 

Published on Leave a comment on The More Languages You Know, the Better

 A lot of research has shown benefits to being bilingual (here, here, and here). Now research suggests that knowing even more languages (multilingualism) may be even better for the brain's flexibility or "neural plasticity". From Science Daily:

EEG recordings prove learning foreign languages can sharpen our minds

Scientists from the Higher School of Economics (HSE) together with colleagues from the University of Helsinki have discovered that learning foreign languages enhances the our brain's elasticity and its ability to code information. The more foreign languages we learn, the more effectively our brain reacts and processes the data accumulated in the course of learning. 

Researchers carried out experiments where the brain's electrical activity was measured with EEG (electroencephalography). Twenty-two students in total (10 male and 12 female) participated in the investigation, with the average age being 24. The subjects had electrodes placed on their heads and then listened to recordings of different words in their native language, as well in foreign languages, both known and completely unknown by the subjects. When the known or unknown words popped up, changes in the brain's activity were tracked.... Apparently, the ability of the brain to quickly process information depends on one's "linguistic anamneses."

The experiment has shown that the brain's electrical activity of those participants who had already known some foreign languages, was higher. The author of the study, Yuriy Shtyrov commented that the more languages someone mastered, the faster the neuron network coding the information on the new words was formed. Consequently, this new data stimulates the brain's physiology: loading the mind with more knowledge boosts its elasticity. 

Published on Leave a comment on Early Childhood Antibiotic Use and Food Allergies

Yikes! Another study showing effects from antibiotic use - this time a higher incidence of food allergies in children who took antibiotics in the first year of life. Especially multiple courses of antibiotics, with the strongest association among children receiving cephalosporin and sulfonamide antibiotics. Antibiotics can be life-saving, but there can also be unintended consequences.

As the researchers wrote: "Changes in the composition, richness, and abundance of microbiota that colonize the human gut during infancy has been theorized to play a role in development in atopic disease, including food allergen sensitization. " And what changes the gut microbes? Antibiotics. Other research suggests that alterations in microbes due to childhood antibiotic use may increase the risk of Crohn's disease, obesity, and asthma. From Science Daily:

Young children's antibiotic exposure associated with higher food allergy risk

Antibiotic treatment within the first year of life may wipe out more than an unwanted infection: exposure to the drugs is associated with an increase in food allergy diagnosis, new research from the University of South Carolina suggests.

Analyzing South Carolina Medicaid administrative data from 2007 to 2009, researchers from the College of Pharmacy, School of Medicine and Arnold School of Public Health identified 1,504 cases of children with food allergies and 5,995 controls without food allergies, adjusting for birth month and year, sex and race/ethnicity. Applying conditional logistic regression and adjusting for factors including birth, breastfeeding, asthma, eczema, maternal age and urban residence, the researchers found that children prescribed antibiotics within the first year of life were 1.21 times more likely to be diagnosed with food allergy than children who hadn't received an antibiotic prescription.

The association between antibiotic prescription and development of food allergy was statistically significant, and the odds of a food allergy diagnosis increased with the number of antibiotic prescriptions a child received, growing from 1.31 times greater risk with three prescriptions to 1.43 times with four prescriptions and 1.64 times with five or more prescriptions. The interdisciplinary research team, led by Bryan Love, Pharm.D., found the strongest association between children who were prescribed cephalosporin and sulfonamide antibiotics, which are broad-spectrum therapies (adjusted OR 1.50 and 1.54, respectively), compared with narrower spectrum agents such as penicillins and macrolides. .

This research builds upon previous studies finding that normal gut flora is critical for developing the body's tolerance to foreign proteins such as food. Antibiotics are known to alter the composition of gut flora, and U.S. children ages three months to three years are prescribed 2.2 antimicrobial prescriptions per year on average, according to the literature. The study's results suggest a potential link between the rise in antibiotic prescriptions for young children and the rise in diagnosis of food allergies in children.