A small (American) public opinion poll shows a shift in favor of medical vaccines

© 2015 Peter Free

Citation

Matthew M. Davis, Sarah J. Clark, Dianne C. Singer, Amilcar Matos-Moreno, and Anna Daly Kauffman, Safer, with more benefits: Parents’ vaccines views shifting, University of Michigan Health System (06 July 2015)

When it comes to dealing with humans . . .

. . .  I imagine that an alien being of reasonable intelligence would see us as constituting a primitive animal experiment in evolution:

In May 2015, we asked parents across the U.S. for their opinions about the benefits and safety of vaccines, compared with one year ago. Parents were also asked about their perceptions of the risk of measles and whooping cough for children in the U.S.

This report presents findings from a nationally representative household survey conducted exclusively by GfK Custom Research . . . .

The survey was administered in May 2015 to a randomly selected, stratified group of parents age 18 and older with at least one child age 0-17 (n =1,416) from GfK’s web-enabled KnowledgePanel® that closely resembles the U.S. population.

The sample was subsequently weighted to reflect population figures from the Census Bureau. The survey completion rate was 55% among panel members contacted to participate. The margin of error is ±2 to 3 percentage points.

Outbreaks of measles and whooping cough in 2014 and early in 2015 have sparked national conversations about the benefits and risks of childhood vaccination. In particular, a multi-state outbreak of measles linked to an amusement park in California in 2015 caused widespread concern. In fact, this outbreak followed 23 separate outbreaks of measles in the U.S. in 2014.

The majority of cases of vaccine-preventable diseases occur in unvaccinated individuals. As a result, many medical professionals and public health experts encourage timely vaccination of children and adolescents. However, some parents remain concerned about potential risks of vaccines for their children and seek exemptions from school and daycare entry requirements that exist in all states.

Compared to one year ago, one-third of parents (34%) believe vaccines have more benefit, 61% say they have about the same benefit and 5% of parents think vaccines have less benefit.

With regard to vaccine safety, one-quarter of parents (25%) believe vaccines are safer than they believed one year ago, 68% say their perceptions of vaccine safety have stayed the same and 7% of parents believe that vaccines are less safe than they believed one year ago.

Compared with one year ago, 35% of parents more strongly support vaccination requirements for daycare and school entry, while 6% are less supportive and 59% say their support has not changed.

Parents were also asked their opinions about the risk of measles and whooping cough, compared with one year ago. Two out of every five parents (40%) believe the risk of measles for children in the U.S. is higher than what it was one year ago, while 45% say the risk is about the same and 15% say the risk of measles is lower than it was one year ago.

Similarly, 37% of parents believe the risk of whooping cough is higher for children than it was one year ago, 49% believe the risk is the same and 15% think the risk is lower.

© 2015 Matthew M. Davis, Sarah J. Clark, Dianne C. Singer, Amilcar Matos-Moreno, and Anna Daly Kauffman, Safer, with more benefits: Parents’ vaccines views shifting, University of Michigan Health System (06 July 2015) (resequenced extracts, underlines added)

Notice the small segment of the public that apparently saw the persuasive evidence for vaccination pointing the other way

Rationally, I suppose, I might conclude that this apparently obtuse group may have been a randomness blip signifying nothing.

The cynic in me, however, happily imagines a group of stalwartly obtuse monkey-brained people still surviving in our civilization’s metaphorical trees.

The moral? — Never underestimate humanity’s capacity for clinging to ignorance

Which arguably equally often simply amounts to ingrained (and/or perhaps newly mutated) stupidity.

Sigh.

Study finds that people with patent foramen ovales do not successfully adjust their O2 transport at altitude — Sounds reasonable, until you recognize that only 21 subjects (including controls) were tested

© 2015 Peter Free

Citation — to study

Jonathan E. Elliott, Steven S. Laurie, Julia P. Kern, Kara M. Beasley, Randall D. Goodman, Bengt Kayser, Andrew W. Subudhi, Robert C. Roach, and Andrew T. Lovering, AltitudeOmics: impaired pulmonary gas exchange efficiency and blunted ventilatory acclimatization in humans with patent foramen ovale after 16 days at 5,260 m, Journal of Applied Physiology 118(9): 1100-1112, DOI: 10.1152/japplphysiol.00879.2014 (01 May 2015)

Citation — to press release

Lewis Taylor, Minor heart condition may come into play at high altitude, says UO team, University of Oregon (26 June 2015)

Did someone skip Statistics 101?

The gist — taken from the press release:

The foramen ovale is a small flap-like opening usually present between the right and left upper chambers of the human heart that normally closes during early infancy. A foramen ovale that doesn’t close is known as a patent foramen ovale, or PFO.

Recent research suggests approximately 40 percent of adult humans have a PFO.

“This seemingly insignificant heart condition had significant impacts on human physiology at high altitude, including reduced breathing response, a reduced ability to oxygenate the blood and increased susceptibility to acute mountain sickness,” said the paper’s co-principal investigator Andrew Lovering, a professor of human physiology.

The study stems from a six-week-long 2012 research expedition involving 15 scientists and 21 subjects, many of them UO students. It is the first such effort to examine the effects of PFO on acclimatization to high altitude.

For their research, Lovering’s nine-member team divided subjects into PFO and non-PFO groups and studied them at rest and during exercise. The tests were performed at sea level, repeated after arriving at a 17,257-foot-high research facility on Bolivia’s Mount Chacaltaya and again after 16 days at altitude.

Researchers recorded gas exchange efficiency — a measure of how well the lung oxygenates the blood. They looked at markers of acclimatization to high altitude such as increased ventilation and reduced incidence of acute mountain sickness.

The team found that PFO subjects did not improve their pulmonary gas exchange efficiency with acclimatization to high altitude — both at rest and while exercising, as non-PFO subjects did — and experienced an increased incidence of acute mountain sickness. Researchers saw little difference between the two groups at sea level and immediately after arriving at altitude.

Forty percent of the PFO subjects were still suffering from acute mountain sickness after five days at altitude, whereas 10 percent of subjects without PFO still had acute mountain sickness at five days.

© 2015 Lewis Taylor, Minor heart condition may come into play at high altitude, says UO team, University of Oregon (26 June 2015) (extracts)

The abstract was worse

It drew conclusions based on probably statistically insupportable findings:

Twenty-one (11 PFO+) healthy sea-level residents were studied at rest and during cycle ergometer exercise at the highest iso-workload achieved at sea level (SL), after acute transport to 5,260 m (ALT1), and again at 5,260 m after 16 days of high-altitude acclimatization (ALT16).

In contrast to PFO− subjects, PFO+ subjects had

1) no improvement in A-aDO2 at rest and during exercise at ALT16 compared with ALT1,

2) no significant increase in resting alveolar ventilation, or alveolar PO2, at ALT16 compared with ALT1,

and consequently had

3) an increased arterial PCO2 and decreased arterial PO2 and arterial O2 saturation at rest at ALT16.

Furthermore, PFO+ subjects had an increased incidence of acute mountain sickness (AMS) at ALT1 concomitant with significantly lower peripheral O2 saturation (SpO2).

These data suggest that PFO+ subjects have increased susceptibility to AMS when not taking prophylactic treatments, that right-to-left shunt through a PFO impairs pulmonary gas exchange efficiency even after acclimatization to high altitude, and that PFO+ subjects have blunted ventilatory acclimatization after 16 days at altitude compared with PFO− subjects.

© 2015 Jonathan E. Elliott, Steven S. Laurie, Julia P. Kern, Kara M. Beasley, Randall D. Goodman, Bengt Kayser, Andrew W. Subudhi, Robert C. Roach, and Andrew T. Lovering, AltitudeOmics: impaired pulmonary gas exchange efficiency and blunted ventilatory acclimatization in humans with patent foramen ovale after 16 days at 5,260 m, Journal of Applied Physiology 118(9): 1100-1112, DOI: 10.1152/japplphysiol.00879.2014 (01 May 2015)

Notice some scientifically critical points

We do not know how many people were controls. How hard would that have been to include in the abstract?

Neither the abstract nor the press release includes p values for the alleged findings. P values measure statistical reliability, thereby allowing us to tentatively eliminate random causation — or, in this case, that the patent foramen ovales had nothing to do with causing what the research team claims to have seen.

Furthermore, no one bothered to explain why anyone should put much stock in the team’s (apparent) observation that:

Forty percent of the PFO subjects were still suffering from acute mountain sickness after five days at altitude, whereas 10 percent of subjects without PFO still had acute mountain sickness at five days.

With regard to this, recognize that we are dealing with only 21 people:

Assuming that there were 11 patent foramen ovales (meaning that the hole between ventricles had not closed) and 10 controls — then presumably 4 of the former had not adjusted to the altitude.

And ten percent of the controls would mean 1 person.

Ergo, this (inferentially) means that:

7 of the patent ovale subjects had (presumably) adjusted to altitude, along with 9 of the controls.

And 4 and 1 had not.

How is this breakdown statistically significant? Especially, when one considers myriad confounding biologic variabilities (between persons) that have no relationship to differences in open or closed foramen ovales.

Did these trivial differences between subjects and controls eliminate the null hypothesis?

I don’t think so. And the team’s abstract does not even raise the subject in quantitative terms.

In fairness, the abstract does say that “these data suggest that  . . . .” But that’s a statistically invalid copout.

For example, when I drop a ball during a thunder storm and thunder sounds 3 out of 10 times, I could opine that “the data” suggested that the ball drop itself may have had something significant to do with the sound blasts in the sky.

The moral? — Good hypothesis, probably valuable data, but overstated conclusions

This may just be a communicatively inferior abstract. But I doubt it.

Our prestige-seeking egos tend to shy away from making appropriately conservative statements like, “This may mean nothing, but our data — such as it is — may be worth following up on.”

Methane found in Mars-origin meteorites — fuels speculation that subsurface methane on Mars might once have fueled life

© 2015 Peter Free

Citation — to study

Nigel J. F. Blamey, John Parnell, Sean McMahon, Darren F. Mark, Tim Tomkinson, Martin Lee, Jared Shivak, Matthew R. M. Izawa, Neil R. Banerjee, and Roberta L. Flemming, Evidence for methane in Martian meteorites, Nature Communications, DOI:10.1038/ncomms8399 (16 June 2015)

Citation — to press release

Jim Shelton, Scientists find methane in Mars meteorites, Yale News (16 June 2015)

The gist

From the press release:

The researchers examined samples from six meteorites of volcanic rock that originated on Mars. The meteorites contain gases in the same proportion and with the same isotopic composition as the Martian atmosphere.

All six samples also contained methane, which was measured by crushing the rocks and running the emerging gas through a mass spectrometer. The team also examined two non-Martian meteorites, which contained lesser amounts of methane.

The discovery hints at the possibility that methane could be used as a food source by rudimentary forms of life beneath the Martian surface. On Earth, microbes do this in a range of environments.

© 2015 Jim Shelton, Scientists find methane in Mars meteorites, Yale News (16 June 2015) (extracts)

Speculation

From the abstract:

Here we show that some Martian meteorites, representing basic igneous rocks, liberate a methane-rich volatile component on crushing.

The occurrence of methane in Martian rock samples adds strong weight to models whereby any life on Mars is/was likely to be resident in a subsurface habitat, where methane could be a source of energy and carbon for microbial activity.

© 2015 Nigel J. F. Blamey, John Parnell, Sean McMahon, Darren F. Mark, Tim Tomkinson, Martin Lee, Jared Shivak, Matthew R. M. Izawa, Neil R. Banerjee, and Roberta L. Flemming, Evidence for methane in Martian meteorites, Nature Communications, DOI:10.1038/ncomms8399 (16 June 2015) (paragraph split)

A dose of reality

First, notice that non-Martian meteorites also contained methane.

Second, just because an ingredient for a hypothetical life-generation model is present, does not mean that the model itself makes sense under conditions we know virtually nothing about.

The moral? — Mars continues to span enthusiastic imaginings on Earth

Remember Martian canals?

An industry-connected rat study — demonstrated that commonly used linear gadolinium-based MRI contrast agents — leave toxic heavy metal traces in brain’s deep cerebellar nuclei — Researcher predicts a switch to macrocyclic gadolinium contrast substitute that leaves no such traces

© 2015 Peter Free

Citation — to study

Philippe Robert,  Stéphane  Lehericy, Sylvie Grand, Xavier Violas, Nathalie Fretellier, Jean-Marc Idée, Sébastien  Ballet, and  Claire Corot, T1-Weighted Hypersignal in the Deep Cerebellar Nuclei After Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats: Difference Between Linear and Macrocyclic Agents, Investigative Radiology, DOI: 10.1097/RLI.0000000000000181 (published online ahead of print, 22 June 2015)

Citation — to press release

Connie Hughes, Study Highlights ‘Important Safety Issue’ with Widely Used MRI Contrast Agents, Wolters Kluwer Health (25 June 2015)

The gist

From the press release:

The study adds to concerns that repeated use of specific “linear”-type gadolinium-based contrast agents (GBCAs) lead to deposits of the heavy-metal element gadolinium in the brain.

The results will have a major impact on the multimillion-dollar market for MRI contrast agents, predicts Investigative Radiology Editor-in-Chief Val M. Runge, MD, of University Hospital Zurich.

He comments, “This important safety issue may lead to certain linear GBCAs not being used in the future.”

Led by Philippe Robert, PhD, of the French pharmaceutical company Guerbet, the researchers designed experiments in rats to assess the effects of repeated injections of GBCAs. These agents are widely used for diagnostic MRI scans, with approximately 30 million doses given each year worldwide.

Over five weeks, one group of rats received a series of 20 injections with gadodiamide, one of a class of agents known as “linear” GBCAs.

Another group of animals were injected with a different type of GBCA—the “macrocyclic” agent gadoterate meglumine. (Dr. Robert’s company, Guerbet, manufactures gadoterate meglumine.)  A third group of rats received an inactive saline solution.

Over time, “significant and persistent” MRI abnormalities (called T1-weighted signal hyperintensities) developed in the brains of rats receiving the linear GBCA, gadodiamide. But no MRI abnormalities appeared in the brains of rats injected with the macrocyclic agent, gadoterate meglumine.

The increases in signal hyperintensity persisted even after the injections stopped.

In subsequent examinations, high total gadolinium concentrations were measured in the deep brain (cerebellum) of gadodiamide-treated rats, corresponding to the area of the MRI abnormalities.

The findings are consistent with recent studies reporting T1 hyperintensities in human patients receiving multiple injections of linear GBCAs for MRI scans.

“Certain of these agents lead to heavy-metal deposition in parts of the brain, which is not seen with the macrocyclic GBCAs,” says Dr. Runge.

A pioneer in the development of chelated gadolinium as a contrast agent for MRI, Dr. Runge was the first to publicly propose the concept in 1982. In 1984, he demonstrated the effectiveness of the first GBCA to be developed, which was approved in 1988.

© 2015 Connie Hughes, Study Highlights ‘Important Safety Issue’ with Widely Used MRI Contrast Agents, Wolters Kluwer Health (25 June 2015) (extracts)

Caveat

Given the financial interest of the research-sponsoring manufacturer, corroborating research will be necessary to overcome suspicions of inadvertent bias in methodology, implementation and/or analysis.

The moral? — A concerning finding, no matter who sponsored the contrast agent research

And a warning that — just because something is routinely done, does not mean it is either safe or representative of an arguably wise prioritization of risks.

A small study at just one urban emergency room — showed that it over diagnosed women with urinary tract infections (UTIs) — by roughly two fold — and significantly underdiagnosed sexually transmitted infections (STIs) in the same patients — by about 37 percent — The failure to bacteriologically culture urine apparently contributed to these mistakes

© 2015 Peter Free

Citation — to study

Myreen E. Tomas, Damon Getman, Curtis J. Donskey, and Michelle T. Hecker, Over-Diagnosis of Urinary Tract Infection and Under-Diagnosis of Sexually Transmitted Infection in Adult Women Presenting to an Emergency Department, Journal of Clinical Microbiology, DOI: 10.1128/JCM.00670-15 (accepted manuscript, early online publication, 10 June 2015)

Citation — to press release

American Society for Microbiology, In ERs, UTIs and STIs in women misdiagnosed, even mixed up nearly half the time, ScienceDaily (24 June 2015)

The gist

From the American Society for Microbiology:

Urinary tract and sexually transmitted infections in women are misdiagnosed by emergency departments nearly half the time, according to a paper in the Journal of Clinical Microbiology . . . .

These misdiagnoses result in overuse of antibiotics, and increased antibiotic resistance, according to Michelle Hecker . . . and her collaborators.

“Less than half the women diagnosed with a urinary tract infection actually had one,” said Hecker.

“Sexually transmitted infections were missed in 37 percent of the women, many of whom were wrongly diagnosed with urinary tract infections.”

The results, she said, indicate that emergency department diagnostic testing strategies for both types of infection need to be re-evaluated.

The study examined records from 264 women, ages 18-65, who were seen at the MetroHealth Medical Center emergency department.

The investigators were able to retrieve urine samples the women had provided, and to test these for the sexually transmitted infections gonorrhea, chlamydia, and trichomonas in cases where these tests had not been ordered as part of routine care.

© 2015 American Society for Microbiology, In ERs, UTIs and STIs in women misdiagnosed, even mixed up nearly half the time, ScienceDaily (24 June 2015) (extracts)

Background — regarding medical jargon and techniques

Empiric treatment in medicine, especially with regard to infections, means initiating therapy based on clinical signs and symptoms, without first testing to ensure that one’s presumed diagnosis is correct.

This can be problematic, when different kinds (or locations) of infections — and the organisms that cause them — manifest in pretty much the same way.

In reading the below extracts from the study, understand that urine analysis (UA) and urine culture (UC) are not the same thing.

The former looks for already present signs of the patient’s immune system response to an infection. These immune responses are not definitive because the immune system only as a handful of ways of doing anything. Thus, even “you are sick” quantities of immune traces in one’s urine are not a reliable ways of being sure exactly what is causing the specific problem.

In contrast, urine culture attempts to grow a sample of the specific “bad guy” organism.  This usually takes days, and most physicians and patients would prefer not to wait so long.

In the ideal world, an amplified urine nucleic acid (DNA/RNA) analysis could shortcut the time that it takes to culture the actual organism. Traces of the culprit microorganism’s DNA/RNA are artificially (but reliably) multiplied — so as to generate enough material to make an exact diagnosis of the infectious agent.

However, a significant remaining advantage to actual culture is that the one can test what has grown to see which antibiotics will kill or inhibit it. Unfortunately, empiric treatment with antibiotics (meaning before culture) usually means that the subsequent cultured sample is so screwed up that it becomes unreliable.

Part of what the research team found was that urine analyses (UAs) are not reliable in confirming the presence of urinary tract infections

From the abstract:

We conducted a 2-month observational cohort study to determine the accuracy of clinical diagnoses of UTI and STI in adult women presenting with genitourinary (GU) symptoms or diagnosed with GU infections at an urban academic ED.

For all urine specimens, UA [urine analysis], culture, and nucleic acid amplification testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis were performed.

Of 264 women studied, providers diagnosed 175 (66%) with UTI, 100 (57%) of whom were treated without performing a urine culture during routine care.

Combining routine care and study-performed urine cultures, only 84 (48%) of these women [actually] had a positive urine culture.

Sixty (23%) of all 264 women studied had one or more positive STI tests, 22 (37%) of whom did not receive STI treatment within 7 days of the ED visit.

Fourteen (64%) of these 22 women were diagnosed with a UTI instead of an STI.

[E]mpiric therapy for UTI without urine culture testing and over-diagnosis of UTI were common and associated with unnecessary antibiotic exposure and missed STI diagnoses.

© 2015 Myreen E. Tomas, Damon Getman, Curtis J. Donskey, and Michelle T. Hecker, Over-Diagnosis of Urinary Tract Infection and Under-Diagnosis of Sexually Transmitted Infection in Adult Women Presenting to an Emergency Department, Journal of Clinical Microbiology, DOI: 10.1128/JCM.00670-15 (accepted manuscript, early online publication, 10 June 2015) (at Abstract) (extracts, underlines added)

And here’s a mild surprise — sloppy medicine?

From the body of the paper:

Twenty-four percent of subjects diagnosed with UTI had no possible UTI-related symptoms documented.

Although in several reviews of uncomplicated UTI . . . empiric therapy without urine culture is recommended for women with suspected uncomplicated cystitis [bladder irritation] presenting with at least 1 traditional lower UTI symptom and without vaginitis [vaginal inflammation] symptoms or other complicating factors, we noted that empiric therapy without urine culture was often prescribed for subjects without this combination of symptoms.

© 2015 Myreen E. Tomas, Damon Getman, Curtis J. Donskey, and Michelle T. Hecker, Over-Diagnosis of Urinary Tract Infection and Under-Diagnosis of Sexually Transmitted Infection in Adult Women Presenting to an Emergency Department, Journal of Clinical Microbiology, DOI: 10.1128/JCM.00670-15 (accepted manuscript, early online publication, 10 June 2015) (at PDF lines 248-253) (extracts, underlines added)

The problem with relying on urine analyses — rather than on urine cultures

The authors pointed out that:

Although an abnormal UA (mostly related to the presence of pyuria or positive leukocyte esterase) may occur with STI [sexually transmitted infection], collection contamination, and asymptomatic bacteriuria,

providers frequently appeared to [erroneously] equate an abnormal UA with the diagnosis of a UTI.

This misinterpretation of an abnormal UA and the suboptimal performance characteristics of the UA in predicting a positive urine culture in this population likely contributed to over-diagnosis of UTI and under-diagnosis of STI.

We believe the current clinical practice of empiric therapy for suspected lower UTI (cystitis) without urine culture may be penny wise but pound foolish.

Although there may be cost savings from not performing urine cultures, the costs of unnecessary antibiotic therapy and missed STI diagnoses, may be greater, given concerns for [:]

increasing resistance to both uropathogens and N. gonorrhoeae,

adverse effects due to unnecessary antibiotic therapy,

and

the clinical and public health consequences of unrecognized and untreated STI (risk for sexual partner infection, and increase risk of pelvic inflammatory disease, adhesions, ectopic pregnancy, infertility, and chronic pelvic pain).

© 2015 Myreen E. Tomas, Damon Getman, Curtis J. Donskey, and Michelle T. Hecker, Over-Diagnosis of Urinary Tract Infection and Under-Diagnosis of Sexually Transmitted Infection in Adult Women Presenting to an Emergency Department, Journal of Clinical Microbiology, DOI: 10.1128/JCM.00670-15 (accepted manuscript, early online publication, 10 June 2015) (at PDF lines 316-326) (extracts, underline added)

Does the fact that this was just one emergency room make a difference?

Probably not. Even for primary care generally.

Empiric therapy, as practiced at least with regard to routinely seen infections, seems to be the norm. My guess is that this study’s findings are roughly indicative of medical practice generally.

In regard to mistaken reliance on urine analyses, I concluded long ago that understanding of the science underlying medicine and medical tests is rife in the field. Most physicians and surgeons are not rigorously scientifically minded, despite the hype surrounding their training. This is one (probably not surprising) aspect of the profession that I noticed during my first year of training.

That said, some of my own bias may have intruded in reaching my hypothesis about the expandability of this study’s finding to primary care at large. I have always thought it stupid to treat unknown organisms with antibiotics that are only slightly less than randomly chosen. (I exaggerate to make the point.)

When we combine (a) the body’s ability to heal itself without intervention with (b) a shotgun approach to medical treatment, we create a morass of unknowns that have possibly hidden and negative downstream effects.

Did our interventions work or not? Because we don’t track very much in the way of cause and effect, we simply do not know.

I think that we take far too much for granted — with the result that we are now about to lose efficacy of the antibiotic therapies that we have taken for granted since the 1950s.

The moral? — Arguably sloppy convenience (probably) does not make good medicine

As the authors put it slightly more diplomatically:

Until a more accurate rapid diagnostic test for UTI is available . . . increasing urine culture and STI testing, and decreasing empiric therapy for suspected UTI or STI in this population should be evaluated.

© 2015 Myreen E. Tomas, Damon Getman, Curtis J. Donskey, and Michelle T. Hecker, Over-Diagnosis of Urinary Tract Infection and Under-Diagnosis of Sexually Transmitted Infection in Adult Women Presenting to an Emergency Department, Journal of Clinical Microbiology, DOI: 10.1128/JCM.00670-15 (accepted manuscript, early online publication, 10 June 2015) (at PDF lines 326-329)