Author: DES Daughter

Foetal oestrogens and autism

High Levels of Sex Hormones in The Womb Linked to Autism Once More

A small new study has once again found a link between elevated hormone levels in the womb and the likelihood of developing autism. But this time, instead of major androgens such as testosterone, researchers are pointing the finger at estrogen, medicalxpress and sciencealert report. Image.

Abstract

Elevated latent prenatal steroidogenic activity has been found in the amniotic fluid of autistic boys, based on measuring prenatal androgens and other steroid hormones. To date, it is unclear if other prenatal steroids also contribute to autism likelihood. Prenatal oestrogens need to be investigated, as they play a key role in synaptogenesis and corticogenesis during prenatal development, in both males and females. Here we test whether levels of prenatal oestriol, oestradiol, oestrone and oestrone sulphate in amniotic fluid are associated with autism, in the same Danish Historic Birth Cohort, in which prenatal androgens were measured, using univariate logistic regression (n = 98 cases, n = 177 controls). We also make a like-to-like comparison between the prenatal oestrogens and androgens. Oestradiol, oestrone, oestriol and progesterone each related to autism in univariate analyses after correction with false discovery rate. A comparison of standardised odds ratios showed that oestradiol, oestrone and progesterone had the largest effects on autism likelihood. These results for the first time show that prenatal oestrogens contribute to autism likelihood, extending the finding of elevated prenatal steroidogenic activity in autism. This likely affects sexual differentiation, brain development and function.

“In conclusion, we have demonstrated that prenatal oestradiol, oestriol and oestrone are elevated in in boys who went on to develop autism. This extends our previous finding of elevated prenatal steroidogenesis in the same cohort and provides further evidence for the prenatal steroid theory of autism. High levels of prenatal oestradiol contribute to a greater degree to autism likelihood than other prenatal sex steroids, including testosterone. We conclude that prenatal oestrogenic excess is a characteristic of autism and may interact with genetic predisposition to affect neurodevelopment.”

See studies in ref to DES and autism, ADHD, Down’s syndrome.

Corruption in the pharmaceutical sector

Diagnosing the challenges, Transparency International UK, 2016

Summary

Within the health sector, pharmaceuticals stands out as sub-sector that is particularly prone to corruption. There are abundant examples globally that display how corruption in the pharmaceutical sector endangers positive health outcomes. Whether it is a pharmaceutical company bribing a doctor for prescribing its medicines irrespective of a health need or a government employee facilitating the infiltration of substandard medicines into the distribution system, public resources can be wasted and patient health put at risk.

For policy makers to implement successful anti-corruption measures there is a need to identify and understand corruption vulnerabilities in the pharmaceutical sector. To support this task this paper identifies key policy and structural issues in selected activities of the pharmaceutical value chain, along with relevant anti-corruption policies. This analysis showed that anti-corruption policies are needed throughout the pharmaceutical value chain to increase transparency around key decision points and strengthen the accountability of actors.

Four overarching challenges derived from structural issues and anti-corruption policies across the selected activities of the value chain have been identified. These are:

  • A lack of objective data and understanding of corruption inhibited by environmental context, the complexity of issues in the sector and policy makers not viewing corruption as an issue.
  • A weak legislative and regulatory framework because of poor investment, a lack of oversight and national regulatory frameworks that are often decentralised and reliant on self-regulation for key decision-point.
  • The potential for undue influence from companies due to a high degree of autonomy over key decision points and unparalleled resources, on policy and regulation so profit maximisation goes beyond ethical norms and negatively impacts health outcomes and public health objectives.
  • A lack of leadership committed to anti-corruption efforts from all actors. National leaders often only implement reforms after a crisis, with their inaction regularly hindering other actors.

Similarly, three key action areas to mitigate corruption vulnerabilities in the pharmaceutical sector are examined. These include establishing leadership committed to addressing corruption, adopting technology throughout the value chain and ensuring accountability through increased monitoring, enforcement and sanctions.

These overarching challenges and action areas are neither novel nor resource-intensive, stressing the lack of effective action in the past; as well as the difficulty of dealing with corruption in a sector that is extremely complex, has a high level of government intervention and often has regulatory systems in place that are inadequate to properly govern the value chain. Only by overcoming these challenges and focusing on these action areas will the global health community be better able to meet the health Sustainable Development Goals.

The Myth of Scientific Objectivity

Dr. Terence Kealey during a CrossFit Health event on March 9, 2019

“I think there is a vast myth that scientists are somehow objective and honest.”

~Dr. Terence Kealey~

Kealey is a former vice-chancellor of the University of Buckingham, a professor of clinical biochemistry, a scholar affiliated with the Cato Institute, and author of the book Breakfast Is a Dangerous Meal. During his presentation, he discussed the myth of scientific objectivity, drawing examples widely from history as well as his personal experiences within many of the most reputable scientific institutions.

Video published on 12 Aug 2019. Reference. Full transcript.

Primodos survivors take on drugs firm

Primodos: Firms and govt face legal action over claims pregnancy drug ‘damaged babies’, Sky News, Aug 2019

“Parents who say their babies were damaged by a pregnancy test drug have warned manufacturers and the government that they are preparing to take legal action.”

Primodos, a pregnancy test drug, has led to a decades-long campaign by parents and children who claim it has caused a range of devastating birth defects.

In 2017, Sky News revealed how documents were destroyed and information withheld about the drug that may have deformed and killed babies in the womb.

Now, parents who say their babies were damaged by the drug have warned manufacturers and the government they are preparing to take legal action.

Lawyers representing more than 200 claimants accuse two drug companies and UK regulators of putting patients at risk.

More information

Declining malformation rates with changed antiepileptic drug prescribing – An observational study

Reducing birth defects in women with epilepsy : prescribing responsively leading to results – Aug 2019

Abstract

Objective
Changes in prescribing patterns of antiepileptic drugs (AEDs) in pregnant women with epilepsy would be expected to affect the risk of major congenital malformations (MCMs). To test this hypothesis, we analyzed data from an international pregnancy registry (EURAP).

Methods
EURAP is an observational prospective cohort study designed to determine the risk of MCMs after prenatal exposure to AEDs. The Cochrane-Armitage linear trend analysis was used to assess changes in AED treatment, prevalence of MCMs, and occurrence of generalized tonic-clonic seizures (GTCs) over 3 time periods: 2000–2005 (n = 4,760), 2006–2009 (n = 3,599), and 2010–2013 (n = 2,949).

Results
There were pronounced changes in the use of specific AEDs over time, with a decrease in the use of valproic acid and carbamazepine and an increase in the use of lamotrigine and levetiracetam. The prevalence of MCMs with monotherapy exposure decreased from 6.0% in 2000–2005 to 4.4% in 2010–2013. The change over time in MCM frequency after monotherapy exposure showed a significant linear trend in the crude analysis (p = 0.0087), which was no longer present after adjustment for changes in AED treatment (p = 0.9923). There was no indication of an increase over time in occurrence of GTCs during pregnancy.

Conclusions
There have been major changes in AED prescription patterns over the years covered by the study. In parallel, we observed a significant 27% decrease in the prevalence of MCMs. The results of adjusting the trend analysis for MCMs for changes in AED treatment suggest that changes in prescription patterns played a major role in the reduction of teratogenic events.

Spin in Published Biomedical Literature : A Systematic Review

Medical research publications : how to modify (abstracts) perception of results

Quinn Grundy presents original research that explores the nature and prevalence of spin in the biomedical literature. Video published on 11 Oct 2017. Reference.

Objective
To explore the nature and prevalence of spin in the biomedical literature.

Design
In a systematic review and meta-analysis, we searched MEDLINE, PreMEDLINE, Embase, Scopus, and handsearched reference lists for all articles published between 1946 and 24 November 2016 that included the quantitative measurement of spin in the biomedical literature for at least 1 outcome. Two independent coders extracted data on the characteristics of articles and included studies, methods for assessing spin, and all spin-related results. The data were heterogeneous; results were grouped inductively into outcome-related categories. We had sufficient data to use meta-analysis to analyze the association of industry sponsorship of research with the presence of spin.

Results
We identified 4219 articles after removing duplicates and included 35 articles that investigated spin: clinical trials (23/35, 66%); observational studies (7/35, 20%); diagnostic accuracy studies (2/35, 6%); and systematic reviews and meta-analyses (4/35, 11%), with some articles including multiple study designs. The nature and manifestations of spin varied according to study design. We grouped results into the following categories: prevalence of spin, level of spin, factors associated with spin, and effects of spin on readers’ interpretations. The highest, but also greatest variability in the prevalence of spin was present in trials (median, 57% of main texts containing spin; range, 19%-100% across 16 articles). Source of funding was hypothesized to be a factor associated with spin; however, the meta-analysis found no significant association, possibly owing to the heterogeneity of the 7 included articles.

Conclusions
Spin appears to be common in the biomedical literature, though this varies by study design, with the highest rates found in clinical trials. Spin manifests in diverse ways, which challenged investigators attempting to systematically identify and document instances of spin. Widening the investigation of factors contributing to spin from characteristics of individual authors or studies to the cultures and structures of research that may incentivize or deincentivize spin, would be instructive in developing strategies to mitigate its occurrence. Further research is also needed to assess the impact of spin on readers’ decision making. Editors and peer reviewers should be familiar with the prevalence and manifestations of spin in their area of research to ensure accurate interpretation and dissemination of research.

Soutenez Daniel Cueff, maire courageux, contre les pesticides à proximité des habitations

Paradoxalement, un maire a pris un risque juridique en protégeant ses administrés

“Ne doutez jamais qu’un petit groupe de personnes peuvent changer le monde. En fait, c’est toujours ainsi que le monde a changé.”

~Margaret Mead~

Le 18 mai dernier, Daniel Cueff, maire de Langouët en Bretagne a signé un arrêté interdisant l’épandage de pesticides “à une distance inférieure à 150 m de toute parcelle cadastrale comprenant un bâtiment à usage d’habitation ou professionnel“. Un mois plus tard, la préfecture de Bretagne a fait savoir qu’elle souhaitait casser cette décision.
Vidéo publiée le 08.08.2019 par agir pour l’environnement.

  • Soutenez le maire de Langouët sur agirpourlenvironnement, sur change. ou sur mes opinions.
  • Pesticides. En Ille-et-Vilaine, le maire de Langouët tient tête à la préfète de Bretagne, ouest-france, 25/06/2019. Lire la réponse du maire.
  • Daniel Cueff, le maire breton qui invente le village de l’après-pétrole, Le Monde, 19 juin 2019.
  • Arrêté contre les pesticides en Bretagne. C’est le tribunal administratif qui devra trancher, ouest-france, 11/06/2019.
  • Bretagne. La préfecture demande au maire de Langouët de retirer son arrêté contre les pesticides, ouest-france, 11/06/2019.
  • Pesticides à Langouët : un arrêté discutable mais une opportunité, selon la Conf’paysanne, ouest-france, 04/06/2019.
  • Langouët, village breton 100 % écolo, veut interdire les pesticides, ouest-france, 23/05/2019.
  • Ille-et-Vilaine. Le maire de Langouët interdit les pesticides près des habitations, ouest-france, 18/05/2019.

Identification of Spin in Clinical Studies Evaluating Biomarkers in Ovarian Cancer

Medical research publications : how to modify (abstracts) perception of results

Mona Ghannad presents a systematic review which documents and classifies spin or overinterpretation, as well as facilitators of spin, in recent clinical studies evaluating performance of biomarkers in ovarian cancer. Video published on 11 Oct 2017. Reference.

Objective
The objective of this systematic review was to document and classify spin or overinterpretation, as well as facilitators of spin, in recent clinical studies evaluating performance of biomarkers in ovarian cancer.

Design
We searched PubMed systematically for all studies published in 2015. Studies eligible for inclusion described 1 or more trial designs for identification and/or validation of prognostic, predictive, or diagnostic biomarkers in ovarian cancer. Reviews, animal studies, and cell line studies were excluded. All studies were screened by 2 reviewers. To document and characterize spin, we collected information on the quality of evidence supporting the study conclusions, linking the performance of the marker to outcomes claimed.

Results
In total, 1026 potentially eligible articles were retrieved by our search strategy, and 345 studies met all eligibility criteria and were included. The first 200 studies, when ranked according to publication date, will be included in our final analysis. Data extraction was done by one researcher and validated by a second. Specific information extracted and analyzed on study and journal characteristics, key information on the relevant evidence in methods, and reporting of conclusions claimed for the first 50 studies is provided here. Actual forms of spin and facilitators of spin were identified in studies trying to establish the performance of the discovered biomarker.

Actual forms of spin identified as shown (Table) were:

  1. other purposes of biomarker claimed not investigated (18 of 50 studies [36%]);
  2. incorrect presentation of results (15 of 50 studies [30%]);
  3. mismatch between the biomarker’s intended clinical application and population recruited (11 of 50 studies [22%]);
  4. mismatch between intended aim and conclusion (7 of 50 studies [14%]);
  5. and mismatch between abstract conclusion and results presented in the main text (6 of 50 studies [12%]).

Frequently observed facilitators of spin were:

  1. not clearly prespecifying a formal test of hypothesis (50 of 50 studies [100%]);
  2. not stating sample size calculations (50 of 50 studies [100%]);
  3. not prespecifying a positivity threshold of continuous biomarker (17 of 43 studies [40%]);
  4. not reporting imprecision or statistical test for data shown (ie, confidence intervals, P values) (12 of 50 studies [24%]);
  5. and selective reporting of significant findings between results for primary outcome reported in abstract and results reported in main text (9 of 50 studies [18%]).

Conclusions
Spin was frequently documented in abstracts, results, and conclusions of clinical studies evaluating performance of biomarkers in ovarian cancer. Inflated and selective reporting of biomarker performance may account for a considerable amount of waste in the biomarker discovery process. Strategies to curb exaggerated reporting are needed to improve the quality and credibility of published biomarker studies.

Toxic Soup Flooding Through Consumer Products and Toys Made of Recycled Plastics

High Levels of Dioxins Found in Children’s Toys and Other Products Made of Recycled Plastics Found in Argentina, Brazil, Cambodia, Canada, the EU, India, Japan and Nigeria

Despite being largely phased out a decade ago because of their adverse health effects, PBDEs continue to show up in everyday products made from recycled plastics, ensia reports.

Alarming levels of some of the most toxic chemicals, including brominated dioxins and brominated flame retardants, were found in consumer products made of recycled plastics sold in Argentina, Brazil, Cambodia, Canada, the EU, India, Japan and Nigeria, ipen says. Dioxins were measured in children’s toys and hair accessories at levels comparable to those found in hazardous wastes, including the ash from waste incinerators, ipen reports.

Systematic reviews with financial conflicts of interest linked to favourable conclusions and lower methodological quality

Financial conflicts of interest in systematic reviews: associations with results, conclusions, and methodological quality

Abstract

Background
Financial conflicts of interest in systematic reviews (e.g. funding by drug or device companies or authors’ collaboration with such companies) may impact on how the reviews are conducted and reported.

Objectives
To investigate the degree to which financial conflicts of interest related to drug and device companies are associated with results, conclusions, and methodological quality of systematic reviews.

Search methods
We searched PubMed, Embase, and the Cochrane Methodology Register for studies published up to November 2016. We also read reference lists of included studies, searched grey literature sources, and Web of Science for studies citing the included studies.

Selection criteria
Eligible studies were studies that compared systematic reviews with and without financial conflicts of interest in order to investigate differences in results (estimated treatment effect and frequency of statistically favourable results), frequency of favourable conclusions, or measures of methodological quality of the review (e.g. as evaluated on the Oxman and Guyatt index).

Data collection and analysis
Two review authors independently determined the eligibility of studies, extracted data, and assessed risk of bias. We synthesised the results of each study relevant to each of our outcomes. For meta‐analyses, we used Mantel‐Haenszel random‐effects models to estimate risk ratios (RR) with 95% confidence intervals (CIs), with RR > 1 indicating that systematic reviews with financial conflicts of interest more frequently had statistically favourable results or favourable conclusions, and had lower methodological quality. When a quantitative synthesis was considered not meaningful, results from individual studies were summarised qualitatively.

Main results
Ten studies with a total of 995 systematic reviews of drug studies and 15 systematic reviews of device studies were included. We assessed two studies as low risk of bias and eight as high risk, primarily because of risk of confounding. The estimated treatment effect was not statistically significantly different for systematic reviews with and without financial conflicts of interest (Z‐score: 0.46, P value: 0.64; based on one study of 14 systematic reviews which had a matched design, comparing otherwise similar systematic reviews). We found no statistically significant difference in frequency of statistically favourable results for systematic reviews with and without financial conflicts of interest (RR: 0.84, 95% CI: 0.62 to 1.14; based on one study of 124 systematic reviews). An analysis adjusting for confounding due to methodological quality (i.e. score on the Oxman and Guyatt index) provided a similar result. Systematic reviews with financial conflicts of interest more often had favourable conclusions compared with systematic reviews without (RR: 1.98, 95% CI: 1.26 to 3.11; based on seven studies of 411 systematic reviews). Similar results were found in two studies with a matched design, which therefore had a reduced risk of confounding. Systematic reviews with financial conflicts of interest tended to have lower methodological quality compared with systematic reviews without financial conflicts of interest (RR for 11 dimensions of methodological quality spanned from 1.00 to 1.83). Similar results were found in analyses based on two studies with matched designs.

Authors’ conclusions
Systematic reviews with financial conflicts of interest more often have favourable conclusions and tend to have lower methodological quality than systematic reviews without financial conflicts of interest. However, it is uncertain whether financial conflicts of interest are associated with the results of systematic reviews. We suggest that patients, clinicians, developers of clinical guidelines, and planners of further research could primarily use systematic reviews without financial conflicts of interest. If only systematic reviews with financial conflicts of interest are available, we suggest that users read the review conclusions with skepticism, critically appraise the methods applied, and interpret the review results with caution.