Thoughts on the Apple Heart Study

The preliminary findings of the Apple watch heart study were announced this weekend: see this link. This study, paid for by Apple and run via the Stanford Medical School, found a 0.5% incidence of previously undiagnosed episodic atrial fibrillation via Apple Watch, a finding which was confirmed with patch type cardiac monitoring in 84 per cent of cases. The Apple Watch algorithm was calculated to have a 71% positive predictive value for intermittent atrial fibrillation.

Atrial fibrillation is a known risk factor for stroke from cerebral embolism. The incidence of stroke in intermittent atrial fibrillation can be reduced by 70% with the use of anticoagulation medication. Thus, finding cases of atrial fibrillation in the general population and considering treating them with anti-coagulation may be of significant value.

One issue that has not yet been decided is whether the population of people with an Apple Watch is comparable to the populations studied when warfarin was found superior to aspirin. Those populations were often in higher risk groups for stroke than wearers of the Apple Watch might be. The incidence of occult atrial fibrillation is thought to be "0.5 per 1,000 person-years before age 50 to 9.7 per 1,000 person-years after age 70." Is treatment then indicated in people in whom consumer electronics shows a rare episode of atrial fibrillation? Or will we find that persons with rare episodes of atrial fibrillation are more common than previously known, and that such persons as a whole do not need anticoagulant treatment, when in some future decade most mass produced clothing will be able to monitor vital signs? Time will tell.

Taste pathways in mice show crossactivation of some taste and some pain pathways.

For the foraging wild mouse, bitter tastes are often alkaloids in food which may be poisonous. So it is not surprising that it may be of value for a mouse to avoid bitter food as if eating it hurt.

What is more intriguing for us humans would be what a similar pathway might mean about the intersection of heat and flavor in hot tasting cuisines.

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ABSTRACT

Mouse Parabrachial Neurons Signal a Relationship between Bitter Taste and Nociceptive Stimuli

Jinrong Li and Christian H. Lemon

Journal of Neuroscience 27 February 2019, 39 (9) 1631-1648; DOI: https://doi.org/10.1523/JNEUROSCI.2000-18.2018

Taste and somatosensation both mediate protective behaviors. Bitter taste guides avoidance of ingestion of toxins while pain sensations, such as noxious heat, signal adverse conditions to ward off harm. Although brain pathways for taste and somatosensation are typically studied independently, prior data suggest that they intersect, potentially reflecting their common protective role. To investigate this, we applied electrophysiologic and optogenetic techniques in anesthetized mice of both sexes to evaluate relationships between oral somatosensory and taste activity in the parabrachial nucleus (PbN), implicated for roles in gustation and pain. Spikes were recorded from taste-active PbN neurons tested with oral delivery of thermal and chemesthetic stimuli, including agonists of nocisensitive transient receptor potential (TRP) ion channels on somatosensory fibers. Gustatory neurons were also tested to follow electrical pulse stimulation of an oral somatosensory region of the spinal trigeminal subnucleus caudalis (Vc), which projects to the PbN. Neurons composed classic taste groups, including sodium, electrolyte, appetitive, or bitter cells. Across groups, most neurons spiked to Vc pulse stimulation, implying that trigeminal projections reach PbN gustatory neurons. Among such cells, a subpopulation responsive to the bitter taste stimuli quinine and cycloheximide, and aversive concentrations of sodium, cofired to agonists of nocisensitive TRP channels, including capsaicin, mustard oil, and noxious heat. Such neurons populated the lateral PbN. Further, nociceptive activity in PbN bitter taste neurons was suppressed during optogenetic-assisted inhibition of the Vc, implying convergent trigeminal input contributed to such activity. Our results reveal a novel role for PbN gustatory cells in cross-system signaling related to protection.

SIGNIFICANCE STATEMENT Prior data suggest that gustatory and trigeminal neural pathways intersect and overlap in the parabrachial area. However, no study has directly examined such overlap and why it may exist. Here we found that parabrachial gustatory neurons can receive afferent projections from trigeminal nuclei and fire to oral nociceptive stimuli that excite somatosensory receptors and fibers. Activation to aversive nociceptive stimuli in gustatory cells was associated with responding to behaviorally avoided bitter tastants. We were further able to show that silencing trigeminal projections inhibited nociceptive activity in parabrachial bitter taste neurons. Our results imply that in the parabrachial area, there is predictable overlap between taste and somatosensory processing related to protective coding and that classically defined taste neurons contribute to this process.

No autism risk with MMR vaccine, again.

Yet another study NOT funded by industry that ONCE AGAIN shows NO increased risk of autism with immunization. In fact, the (non-significant however) risk ratio, 0.93, was in fact in favor of the vaccine PROTECTING against autism by decreasing the risk by 7%.

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ABSTRACT

Published: Ann Intern Med. 2019.

DOI: 10.7326/M18-2101

ORIGINAL RESEARCH |5 MARCH 2019

Measles, Mumps, Rubella Vaccination and Autism: A Nationwide Cohort Study

Anders Hviid, DrMedSci; Jørgen Vinsløv Hansen, PhD; Morten Frisch, DrMedSci; Mads Melbye, DrMedSci

Background: The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine uptake.

Objective: To evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, or time periods after vaccination.

Design: Nationwide cohort study.

Setting: Denmark.

Participants: 657 461 children born in Denmark from 1999 through 31 December 2010, with follow-up from 1 year of age and through 31 August 2013.

Measurements:

Danish population registries were used to link information on MMR vaccination, autism diagnoses, other childhood vaccines, sibling history of autism, and autism risk factors to children in the cohort. Survival analysis of the time to autism diagnosis with Cox proportional hazards regression was used to estimate hazard ratios of autism according to MMR vaccination status, with adjustment for age, birth year, sex, other childhood vaccines, sibling history of autism, and autism risk factors (based on a disease risk score).

Results:

During 5 025 754 person-years of follow-up, 6517 children were diagnosed with autism (incidence rate, 129.7 per 100,000 person-years). Comparing MMR-vaccinated with MMR-unvaccinated children yielded a fully adjusted autism hazard ratio of 0.93 (95% CI, 0.85 to 1.02). Similarly, no increased risk for autism after MMR vaccination was consistently observed in subgroups of children defined according to sibling history of autism, autism risk factors (based on a disease risk score) or other childhood vaccinations, or during specified time periods after vaccination.

Limitation:

No individual medical chart review was performed.

Conclusion:

The study strongly supports that MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination. It adds to previous studies through significant additional statistical power and by addressing hypotheses of susceptible subgroups and clustering of cases.