Distilbène : quelles leçons sociologiques ?

Une expérience médicale et sociale des perturbateurs endocriniens

Programme National de recherche sur les Perturbateurs Endocriniens – Colloque de restitution du 12 avril 2010 – Rennes.

Trajectoires clinique des enfants distilbène

Vivre la maladie : expériences et identités contemporaines

  • Comment n’a-t-on rien appris du distilbène ?
  • Comment personne n’est-il au courant ?
  • Comment les médecins ne savent-ils rien et ne font-ils rien ?
  • Comment les personnes exposées se retrouvent-elles dans des états divers et variés ; le plus souvent de méconnaissance
    • soit de leur statut ?
    • soit des effets de cet éventuel statut ?

Il y a trois facteurs importants limitant la diffusion des connaissances :

  1. L’absence d’identification des problêmes de santé publique et des populations exposées.
  2. Les limites imposées à la production et à la diffusion des connaissances.
  3. Une généralisation tardive ; le distilbène a longtemps été considéré comme un dossier à part

Vidéo publiée le 3 février 2015 par la chaine Paris Diderot.

Suite à leur enquête – Distilbène : quelles leçons sociologiques – menée de 2010 à 2013, Emmanuelle Fillion (EHESP) et Didier Torny (INRA), sociologues, poursuivent leurs travaux et interviennent dans différents colloques.

Emmanuelle Fillion et Didier Torny

Le Distilbène DES, en savoir plus

Diagnostic tests : how to minimise harm

We must develop new diagnostic tests to tackle real health problems, not to generate them

New diagnostic tests: more harm than good, BMJ 2017;358:j3314,
06 January 2016.

Defenders against overdiagnosis, BMJ 2017;358:j3487, 20 July 2017.

Although new diagnostics may advance the time of diagnoses in selected patients, they will increase the frequency of false alarms, overdiagnosis, and overtreatment in others.

Bjorn Hofmann, professor of medical ethics at Norwegian University of Science and Technology, explains how to minimise harm. Press Play > to listen to the recording.

Key messages

  • Innovative technologies and ample venture capital are combining to produce new disease biomarkers and mobile monitoring devices
  • These new diagnostics are technologically advanced but do not automatically provide improvements in clinical care and population health
  • They have the potential to help some but also to increase the frequency of false alarms, overdiagnosis, and overtreatment in others
  • Excessive testing and false alarms may increase healthcare workload and shift clinicians’ focus towards the healthy
  • Misleading feedback at both the population and individual levels tends to favour further market growth
  • Clinicians must provide a strong counterbalance: educating patients, respecting baseline risk, thinking downstream, and expecting misleading feedback

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Sperm concentration has declined more than 50% in less than 40 years

Temporal trends in sperm count : a systematic review and meta-regression analysis

New Meta-analysis finds that among men from North America, Europe and Australia, sperm concentration has declined more than 50% in less than 40 years and points toward importance of further investigation into environmental factors.

Temporal trends in sperm count: a systematic review and meta-regression analysis, by the Hebrew University of Jerusalem, points to an alarming decline in male reproductive health, and suggests worrying implications for male fertility and reproduction. Based on data collected on men from North America, Europe, Australia and New Zealand from 1973 to 2011, the study performed the first ever systematic review and meta-analysis on sperm counts and found a decline of more than 59%, with no sign of levelling off over time. The findings are significant considering that low sperm levels have also been linked with higher risks of hospitalization and death.

2017 Study Abstract

BACKGROUND
Reported declines in sperm counts remain controversial today and recent trends are unknown. A definitive meta-analysis is critical given the predictive value of sperm count for fertility, morbidity and mortality.

OBJECTIVE AND RATIONALE
To provide a systematic review and meta-regression analysis of recent trends in sperm counts as measured by sperm concentration (SC) and total sperm count (TSC), and their modification by fertility and geographic group.

SEARCH METHODS
PubMed/MEDLINE and EMBASE were searched for English language studies of human SC published in 1981–2013. Following a predefined protocol 7518 abstracts were screened and 2510 full articles reporting primary data on SC were reviewed. A total of 244 estimates of SC and TSC from 185 studies of 42 935 men who provided semen samples in 1973–2011 were extracted for meta-regression analysis, as well as information on years of sample collection and covariates [fertility group (‘Unselected by fertility’ versus ‘Fertile’), geographic group (‘Western’, including North America, Europe Australia and New Zealand versus ‘Other’, including South America, Asia and Africa), age, ejaculation abstinence time, semen collection method, method of measuring SC and semen volume, exclusion criteria and indicators of completeness of covariate data]. The slopes of SC and TSC were estimated as functions of sample collection year using both simple linear regression and weighted meta-regression models and the latter were adjusted for pre-determined covariates and modification by fertility and geographic group. Assumptions were examined using multiple sensitivity analyses and nonlinear models.

OUTCOMES
SC declined significantly between 1973 and 2011 (slope in unadjusted simple regression models −0.70 million/ml/year; 95% CI: −0.72 to −0.69; P < 0.001; slope in adjusted meta-regression models = −0.64; −1.06 to −0.22; P = 0.003). The slopes in the meta-regression model were modified by fertility (P for interaction = 0.064) and geographic group (P for interaction = 0.027). There was a significant decline in SC between 1973 and 2011 among Unselected Western (−1.38; −2.02 to −0.74; P < 0.001) and among Fertile Western (−0.68; −1.31 to −0.05; P = 0.033), while no significant trends were seen among Unselected Other and Fertile Other. Among Unselected Western studies, the mean SC declined, on average, 1.4% per year with an overall decline of 52.4% between 1973 and 2011. Trends for TSC and SC were similar, with a steep decline among Unselected Western (−5.33 million/year, −7.56 to −3.11; P < 0.001), corresponding to an average decline in mean TSC of 1.6% per year and overall decline of 59.3%. Results changed minimally in multiple sensitivity analyses, and there was no statistical support for the use of a nonlinear model. In a model restricted to data post-1995, the slope both for SC and TSC among Unselected Western was similar to that for the entire period (−2.06 million/ml, −3.38 to −0.74; P = 0.004 and −8.12 million, −13.73 to −2.51, P = 0.006, respectively).

WIDER IMPLICATIONS
This comprehensive meta-regression analysis reports a significant decline in sperm counts (as measured by SC and TSC) between 1973 and 2011, driven by a 50–60% decline among men unselected by fertility from North America, Europe, Australia and New Zealand. Because of the significant public health implications of these results, research on the causes of this continuing decline is urgently needed.

Sources and Press Releases
  • Temporal trends in sperm count: a systematic review and meta-regression analysis, Hum Reprod Update, doi.org/10.1093/humupd/dmx022, 25 July 2017.
  • New Meta-analysis finds that among men from North America, Europe and Australia, sperm concentration has declined more than 50% in less than 40 years, Health & Environment, 26 July 2017.
  • Featured image credit freemalaysiatoday.

Addressing endocrine disrupting chemicals requires an integrated strategy

It is time to disrupt business as usual and put the health of the current and future generations first

The dangers of endocrine disrupting chemicals (EDCs) for human health and the environment have long been documented and the evidence keeps piling up every day, yet Europe’s approach to this challenge has been lukewarm, writes Genon Jensen, he Executive Director of Health and Environment Alliance (HEAL).

From bisphenol A to cadmium or a whole variety of pesticides, we are all exposed to EDCs. However, as the debacle on the identification criteria of endocrine disruptors for pesticides illustrates, the European approach to this emerging challenge lacks ambition. Not only does it fail to follow the latest scientific developments, but also to acknowledge the societal demands for a transition to safer alternatives.

On 4 July, a European Commission proposal for criteria to identify endocrine disrupting chemicals for pesticides was agreed by representatives of EU governments – the end of a four-year process.

For health and environment advocates, scientists, or public interest groups such as health professionals or non-profit insurers, these criteria have a bitter and toxic taste. Leaving aside the significant corporate lobbying interference in the process, one is struck by the health and economic burden that a lack of ambition and political will result in for society.

According to a conservative estimate, diseases arising from exposure to EDCs weigh at least €163 billion on European public health budgets.

Meanwhile, urine tests and hair samples from populations all across Europe show the presence of chemicals that should not be there in people’s bodies: for instance, a study carried out in France in 2015 found no less than 21 endocrine disruptors’ residues per women tested, including toxic chemicals that have been banned from the market.

Keeping these numbers in mind, addressing the emerging challenges posed by the exposition to endocrine disruptors across their uses (beyond pesticides, from cosmetics to food packages, or toys) based on precaution and consistency appears both an urgent and obvious need.

Unfortunately, the criteria agreed are narrow, insufficient, impractical, and they will make it very difficult – if not impossible – to prove that a pesticide is disrupting the endocrine system.

Why does this matter? Because the higher the burden of the proof and the bigger the loopholes in the identification criteria, the longer the products will remain on the market, leaving people exposed to their effects and weighing heavily on public health budgets.

What should be done now?

The battle over the identification criteria for pesticides is not completely over yet. After the summer, the European Parliament will be asked to vote on the European Commission proposal – either to sign it off or to veto it.

This is an important opportunity for MEPs to echo the existing concerns, give a voice to almost 500,000 citizens who have asked for more protective criteria without being heard. Therefore, MEPs should reject the current criteria and defend an ambitious approach that reflects the latest state of science.

Traces of endocrine disrupting chemicals are found everywhere, including in our bodies, which means that we are all concerned by their effects. The Endocrine Disruption Exchange lists about 1,300 potential EDCs, and many more suspected substances need to be investigated.

While scientists and public interest groups are doing their share to address this emerging challenge, decision-makers should have the courage to take political steps that are already available. This can start in the European Parliament with the rejection of the flawed pesticides criteria.

It is time to disrupt business as usual and put the health of the current and future generations first.

An Investigation
  1. The Manufacture of a Lie.
  2. A Denial of the State of the Science.
  3. The Interference of the United States.
  4. The Discreet but Major Gift to the Pesticides Lobby.
Endocrine Disruptors

Evaluating low-dose toxicity from endocrine active chemicals

Application of Systematic Review Methods in an Overall Strategy for Evaluating Low-Dose Toxicity from Endocrine Active Chemicals

A new report by the National Academies of Sciences, Engineering, and Medicine proposes a strategy that the U.S. Environmental Protection Agency (EPA) should use to evaluate the evidence of adverse human health effects from low doses of exposure to chemicals that can disrupt the endocrine system.

The report’s proposed strategy has three broad steps that can help evaluate evidence of impacts from low-dose chemical exposure:

  • Surveillance
    Surveillance can detect signals of possible health effects by actively monitoring new data, scientific literature, nontraditional information sources, and stakeholder input to ensure health effects are being identified and analyzed on a regular basis.
  • Investigation and Analysis
    To further investigate the signals, the agency should analyze existing data, generate new data to fill gaps, conduct a systematic review of evidence, or integrate evidence from human and animal studies. One or more of these options might be needed to answer questions about potential signals.
  • Action
    Possible actions the agency could take include updating chemical assessments, regularly monitoring for new data, requiring new data or models to reduce uncertainties, or updating toxicity-testing designs and practices. Additional considerations, such as the public health significance and available resources, would also factor into the decision making.

Sources

Endocrine Disruptors

The pitfalls of big data and the cost of missing something

The human insights missing from big data – TEDx Talks, Nov 2016

With stories from Nokia to Netflix to the oracles of ancient Greece, Tricia Wang demystifies big data and identifies its pitfalls, suggesting that we focus instead on “thick data” – precious, unquantifiable insights from actual people – to make the right business decisions and thrive in the unknown.

Use of antibiotics during pregnancy and the risk of major congenital malformations

Clindamycin, doxycycline, quinolones, macrolides and phenoxymethylpenicillin in utero exposure were linked to major congenital malformations

2017 Study Abstract

Introduction
Few studies have investigated the link between individual antibiotics and major congenital malformations (MCMs) including specific malformations owing to small sample size. We aimed – population based cohort study, British Pharmacological Society, 19 July 2017 – to quantify the association between exposure to gestational antibiotic and the risk of MCMs.

Methods
Using the Quebec pregnancy cohort (1998 -2008), we included a total of 139,938 liveborn singleton alive whose mothers were covered by the “Régie de l’assurance maladie du Québec” drug plan for at least 12 months before and during pregnancy. Antibiotics exposure was assessed in the first trimester and MCMs were identified within the first year of life.

Results
After adjusting for potential confounders, clindamycin exposure was associated with an increased risk of MCMs (aOR 1.34, 95%CI, 1.02-1.77, 60 exposed cases), musculoskeletal system malformations (aOR 1.67, 95%CI, 1.12-2.48, 29 exposed cases) and ventricular/atrial septal defect (aOR 1.81, 95%CI, 1.04-3.16, 13 exposed cases).

Doxycycline exposure increased the risk of circulatory system malformation, cardiac malformations and ventricular/atrial septal defect (aOR 2.38, 95%CI ,1.21-4.67, 9 exposed cases; aOR 2.46, 95%CI, 1.21-4.99, 8 exposed cases; aOR 3.19, 95%CI, 1.57-6.48, 8 exposed cases, respectively). Additional associations were seen with quinolone (1 defect), moxifloxacin (1 defect), ofloxacin (1 defect), macrolide (1 defect), erythromycin (1 defect) and phenoxymethylpenicillin (1 defect). No link was observed with amoxicillin, cephalosporins and nitrofurantoin. Similar results were found when penicillins were used as the comparator group.

Conclusions

  • Clindamycin, doxycycline, quinolones, macrolides and phenoxymethylpenicillin in utero exposure were linked to organ specific malformations.
  • Amoxicillin, cephalosporins and nitrofurantoin were not associated with MCMs.

Late-breaking mutations may play an important role in autism

Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder

Over the past decade, mutations to more than 60 different genes have been linked with autism spectrum disorder (ASD), including de novo mutations, which occur spontaneously and aren’t inherited. But much of autism still remains unexplained.

A new study of nearly 6,000 families implicates a hard-to-find category of de novo mutations: those that occur after conception, and therefore affect only a subset of cells.

2017 Study Abstract

We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 × 10−6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 × 10−3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk.

Sources
  • Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder, Nature Neuroscience, doi:10.1038/nn.4598, 17 July 2017.
  • Late-breaking mutations may play an important role in autism, Boston Children’s Hospital, July 17, 2017.

Epigenetics : Nature v. Nurture

The University of Oslo Faculty of Medicine, 2016

How do the identical twins Lucky Lyle and Troubled Tim end up with different personalities? Is it the environment or genes? Or perhaps both?

Video published by The University of Oslo Faculty of Medicine, 29 Jan 2016.