Another Big Pharma Industry way to bypass EU pharmaceutical legislation in the UK?

UK Ministers have committed to finding new ways to ensure off-patent drugs could be prescribed to patients on the NHS

image of prescription-doctor
The bill on medical innovation would allow doctors to search a database to find drug trials their patients might be eligible to join.

The UK government has thrown its weight behind a private member’s bill to encourage GPs and hospital doctors to try experimental medicines.

Cross-party support for controversial bill to allow doctors to search new database of drug trials despite alarm at risk of diluting safeguards.

UK life sciences minister George Freeman is supporting the bill on medical innovation, which was put forward by Chris Heaton-Harris and is being debated in the House of Commons on Friday.

The bill, which has some cross-party support, would allow doctors to search a database for drugs that are in trials or are licensed for a different use. Opponents are alarmed at any moves to potentially dilute safeguards; it comes shortly after public alarm following the death of one person and six others needing hospital treatment during a drugs trial in France earlier this month. ”

continue reading… Government backs wider access to experimental drugs,
the guardian, 29 January 2016.

Widespread misconception that the benefits of breastfeeding only relate to poor countries

UK ‘world’s worst’ at breastfeeding

breastfeeding-rates
Global distribution of breastfeeding at 12 months Data are from 153 countries between 1995 and 2013. Rates of breastfeeding in the UK are the lowest in the world.

Summary

Breastfeeding in the 21st century: epidemiology, mechanisms, and lifelong effect, the lancet, Volume 387, No. 10017, p475–490, 30 January 2016.

The importance of breastfeeding in low-income and middle-income countries is well recognised, but less consensus exists about its importance in high-income countries.

In the UK, 81% of mothers had tried breastfeeding at some point, but only 34% were breastfeeding at six months and 0.5% at 12 months.

In low-income and middle-income countries, only 37% of children younger than 6 months of age are exclusively breastfed. With few exceptions, breastfeeding duration is shorter in high-income countries than in those that are resource-poor.

Our meta-analyses indicate protection against child infections and malocclusion, increases in intelligence, and probable reductions in overweight and diabetes. We did not find associations with allergic disorders such as asthma or with blood pressure or cholesterol, and we noted an increase in tooth decay with longer periods of breastfeeding. For nursing women, breastfeeding gave protection against breast cancer and it improved birth spacing, and it might also protect against ovarian cancer and type 2 diabetes.

The scaling up of breastfeeding to a near universal level could prevent 823 000 annual deaths in children younger than 5 years and 20 000 annual deaths from breast cancer. Recent epidemiological and biological findings from during the past decade expand on the known benefits of breastfeeding for women and children, whether they are rich or poor.

Soy-rich diet linked to improved success of infertility treatments among EDCs-exposed women

Eating Soy May Protect Women from Health Risks of BPA

soy-products
Consuming soy regularly may protect women who are undergoing infertility treatments from poor success rates linked to bisphenol A exposure, according to a new study.

Eating Soy May Protect Women from Health Risks of BPA, The Endocrine Society,  January 27, 2016

Bisphenol A (BPA) is a chemical found in a variety of food containers, including polycarbonate plastic water bottles and can linings. BPA can mimic estrogen, one of the two main sex hormones found in women. Biomonitoring studies by the U.S. Centers for Disease Control and Prevention estimate that more than 96 percent of Americans have BPA in their bodies.

As of 2014, nearly 100 epidemiological studies have been published tying BPA to health problems, including reproductive disorders, according to the Society and IPEN’s Introduction to Endocrine-Disrupting Chemicals.

“Our study is the first to show a possible interaction between soy and BPA in humans. This is consistent with research in mice that found a soy-rich diet could protect against reproductive health problems associated with BPA exposure. More research is needed to determine why soy has this effect in humans.”

said the new study first author Jorge E. Chavarro, MD, ScD, of Harvard T.H. Chan School of Public Health, Brigham and Women’s Hospital, and Harvard Medical School in Boston, MA.

The researchers examined the relationship between BPA exposure, diet and success rates among 239 women who underwent at least one in vitro fertilization (IVF) cycle at the Massachusetts General Hospital Fertility Center between 2007 and 2012. The women participated in the Environment and Reproductive Health (EARTH) Study, an ongoing prospective cohort study designed to evaluate the role of environmental factors and nutrition in fertility. The EARTH Study was funded by the National Institutes of Health’s National Institute of Environmental Health Sciences.

Soy Intake Modifies the Relation Between Urinary Bisphenol A Concentrations and Pregnancy Outcomes Among Women Undergoing Assisted Reproduction, JCEM, January 27, 2016.

Participants’ urine samples were analyzed to measure BPA exposure. The women, who were between the ages of 18 and 45, completed a lifestyle questionnaire that included questions about how frequently they ate soy-based foods. Among the participants, 176 consumed soy foods.

Among women who did not eat soy foods, those with higher levels of BPA in their urine had lower rates of embryo implantation, fewer pregnancies that progressed to the point where the fetus could be seen on an ultrasound, and fewer live births than women with lower levels of BPA in their bodies. In comparison, BPA concentrations had no impact on IVF outcomes in women who routinely ate soy.

“Although it is recommended that women trying to get pregnant reduce their exposure to BPA, our findings suggest that diet may modify some of the risks of exposure to BPA, a chemical that is nearly impossible to completely avoid due to its widespread use,”

said senior author Russ Hauser, MD, ScD, MPH of Harvard T.H. Chan School of Public Health, Massachusetts General Hospital, Harvard Medical School in Boston, MA.

“Additional research could help identify other diet and lifestyle changes that may modify the effects of not only BPA exposure, but also exposure to other chemicals. In order to fully appreciate risks to human health, we need to design studies that adequately assess both diet and environmental chemical exposures.”

first author Jorge E. Chavarro added.

Association of obesity and diabetes in mothers with autism in children

The research highlights that the risk for autism begins in utero

Obesity-and-Diabete
Children born to obese women with diabetes are more than four times as likely to be diagnosed with autism spectrum disorder than children of healthy weight mothers without diabetes, new Johns Hopkins Bloomberg School of Public Health research suggests.

Abstract

The Association of Maternal Obesity and Diabetes With Autism and Other Developmental Disabilities, Pediatrics, 29 January 2016.

BACKGROUND
Obesity and diabetes are highly prevalent among pregnant women in the United States. No study has examined the independent and combined effects of maternal prepregnancy obesity and maternal diabetes on the risk of autism spectrum disorder (ASD) in parallel with other developmental disorders (DDs).

METHODS
This study is based on 2734 children (including 102 ASD cases), a subset of the Boston Birth Cohort who completed at least 1 postnatal study visit at Boston Medical Center between 1998 and 2014. Child ASD and other DDs were based on physician diagnoses as documented in electronic medical records. Risks of ASD and other DDs were compared among 6 groups defined by maternal prepregnancy obesity and diabetes status by using Cox proportional hazard regression controlling for potential confounders.

Obesity, Diabetes in Mom Increases Risk of Autism in Child, Johns Hopkins Bloomberg School of Public Health, 26-Jan-2016.

RESULTS
When examined individually, maternal prepregnancy obesity and pregestational diabetes (PGDM) were each associated with risk of ASD. When examined in combination, only mothers with obesity and PGDM (hazard ratio 3.91, 95% confidence interval 1.76–8.68) and those with obesity and gestational diabetes (hazard ratio 3.04, 95% confidence interval 1.21–7.63) had a significantly increased risk of offspring ASD. Intellectual disabilities (IDs), but not other DDs, showed a similar pattern of increased risk associated with combined obesity and PGDM. This pattern of risk was mostly accounted for by cases with co-occurring ASD and ID.

CONCLUSIONS
Maternal prepregnancy obesity and maternal diabetes in combination were associated with increased risk for ASD and ID. ASD with ID may be etiologically distinct from ASD without ID.

Antibiotic developed from human breast milk could combat certain drug-resistant bacteria

Breast milk protein could be used in fight against antibiotic resistance

image of breastfeeding
Scientists from NPL and UCL have converted a breast milk protein into an artificial virus that kills bacteria on contact. Breastfeed.

Building antimicrobial viruses from breast milk, National Physical Laboratory, 27 Jan 2016.

As well as providing all the energy and nutrients that infants need for the first months of life, breast milk protects against infectious diseases. Lactoferrin is a protein in milk which provides antimicrobial protection to infants, effectively killing bacteria, fungi and even viruses.

The antimicrobial activities of this protein are mainly due to a tiny fragment, less than a nanometre across, made up of six amino acids. Based on the metrology of antimicrobial mechanisms, the team predicted that copies of this fragment gather at the same time, and at the same point, to attack bacterial cells by targeting and disrupting microbial membranes.

Recognising the potential applications in the fight against antimicrobial resistance, the team of scientists from the National Physical Laboratory (NPL) and the University College London (UCL) re-engineered the fragment into a nanoscale building block which self-assembles into virus-like capsules, to effectively target bacteria. Not only can these capsules recognise and bind to bacteria, but they also rapidly convert into membrane-damaging holes at precise landing positions.

To monitor the activity of the capsules in real time we developed a high-speed measurement platform using atomic force microscopy. The challenge was not just to see the capsules, but to follow their attack on bacterial membranes. The result was striking: the capsules acted as projectiles porating the membranes with bullet speed and efficiency

explains Hasan Alkassem, a joint NPL/UCL EngD student who worked on the project.

Remarkably, however, these capsules do not affect surrounding human cells. Instead, they infected them like viruses do. When viruses are inside human cells they release their genes, which then use the body’s cellular machinery to multiply and produce more viruses. But if viral genes are replaced with drugs or therapeutic genes, viruses become effective tools in the pursuit of gene therapy to cure many diseases, from cancer to cystic fibrosis.

Structurally plastic peptide capsules for synthetic antimicrobial viruses, Chemical Science, 17th December 2015.

The research team explored this possibility and inserted model genes into the capsules. These genes were designed to switch off, or silence, a target process in human cells. The capsules harmlessly delivered the genes into the cells and effectively promoted the desired silencing. With therapeutic genes, this capability could be used to treat disorders resulting from a single mutated gene. Sickle-cell disease, cystic fibrosis or Duchenne muscular dystrophy are incurable at present, but can be cured by correcting corresponding mutated genes. The capsules therefore can serve as delivery vehicles for cures.

Antimicrobial resistance is an increasing public health threat which requires a strong and coordinated response. This work demonstrates the power of combining physics and engineering principles with innovative measurement methods to create new strategies for tackling the problem. It is exactly the sort of high priority problem that the National Physical Laboratory should be active in addressing in collaboration with others.

said Jason Crain, Director of Research at NP.

More press releases
  • Breast milk protein could be used in fight against antibiotic resistance, theguardian, 23 January 2016.
  • Possible solution to antibiotic resistance found in human breast milk, mnn, January 27, 2016.

Suicidality and aggression during SSRI antidepressant treatment

Systematic review and meta-analyses based on clinical study reports

Babel image
Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website. Antidepressant use doubles the risk of suicide in under 18s and the risks to adults may have been seriously underestimated, researchers found. Babel.

Abstract

Suicidality and aggression during antidepressant treatment: systematic review and meta-analyses based on clinical study reports, BMJ 2016;352:i65, 27 January 2016.

Objective
To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.

Design
Systematic review and meta-analysis.

Main outcome measures
Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia.

Data sources
Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website.

Eligibility criteria for study selection
Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms.

Data extraction and analysis
Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model).

Results
We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete.

Antidepressants can raise the risk of suicide, biggest ever review finds, telegraph, 27 January 2016.

Conclusions
Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.

Prenatal exposure to flame retardants linked to poorer behavioral function in children

Children’s mental development could be stunted by chemicals found in couches and upholstery, carpet pads, electronics, some textiles and sofas…

children
New research from the University of Cincinnati (UC) College of Medicine suggests that prenatal exposure to flame retardants and perfluoroalkyl substances (PFASs) commonly found in the environment may have a lasting effect on a child’s cognitive and behavioral development, known as executive function.

Abstract

Maternal Polybrominated Diphenyl Ether (PBDE) Exposure and Thyroid Hormones in Maternal and Cord Sera: The HOME Study, Cincinnati, USA, Environ Health Perspect; DOI:10.1289/ehp.1408996, January 2016.

Background:
Polybrominated diphenyl ethers (PBDEs) reduce blood concentrations of thyroid hormones in laboratory animals, but it is unclear whether PBDEs disrupt thyroid hormones in pregnant women or newborn infants.

Objectives:
We investigated the relationship between maternal PBDE levels and thyroid hormone concentrations in maternal and cord sera.

Methods:
We used data from the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort of 389 pregnant women in Cincinnati, Ohio, who were enrolled from 2003 through 2006 and delivered singleton infants. Maternal serum PBDE concentrations were measured at enrollment (16 ± 3 weeks of gestation). Thyroid hormone concentrations were measured in maternal serum at enrollment (n = 187) and in cord serum samples (n = 256).

Results:
Median maternal serum concentrations of BDEs 28 and 47 were 1.0 and 19.1 ng/g lipid, respectively. A 10-fold increase in BDEs 28 and 47 concentrations was associated with a 0.85-μg/dL [95% confidence interval (CI): 0.05, 1.64] and 0.82-μg/dL (95% CI: 0.12, 1.51) increase in maternal total thyroxine concentrations (TT4), respectively. Both congeners were also positively associated with maternal free thyroxine (FT4). We also observed positive associations between BDE-47 and maternal total and free triiodothyronine (TT3 and FT3). A 10-fold increase in BDE-28 was associated with elevated FT3 concentrations (β = 0.14 pg/mL; 95% CI: 0.02, 0.26). In contrast, maternal PBDE levels were not associated with thyroid hormone concentrations in cord serum.

Conclusions:
These findings suggest that maternal PBDE exposure, particularly BDEs 28 and 47, are associated with maternal concentrations of T4 and T3 during pregnancy.

Prenatal exposure to flame retardants linked to poorer behavioral function in children, sciencedaily, January 27, 2016.

New generation flames retardants chemicals escaping into breathed air at alarming levels

Inhalation is an important route that should be taken into consideration in assessments of flame retardants

MemoryFoam-fast
Researchers report inhalation is an important exposure route for new generation of flame retardant chemicals. Memory foam.

As Washington state decides on stronger toxics law, residents are breathing flame retardants, by Brian Bienkowski, on Environmental Health News, January 25, 2016.

A new generation of chemicals added to furniture, building insulation and baby products like car seats to slow the spread of flames are escaping into air at higher levels than previously thought, according to a new study out of Washington state.

The findings come as Washington lawmakers decide on bolstering flame retardant bans. The state was one of the first to ban an earlier generation of retardants, known as PBDEs.

The new research found flame retardant chemicals used to replace polybrominated diphenyl ethers (PBDEs) also escape, are ubiquitous in indoor air and suggest inhalation is a major route of exposure for people.

The compounds, called chlorinated organophosphate flame retardants, found in the study have been linked to cancer and reproductive problems, and some can alter hormones essential for development.

“We’ve been underestimating what total exposure is”

said Erika Schreder, staff scientist at the Washington Toxics Coalition and lead author of the study published this month in the scientific journal Chemosphere.

Researchers gave 10 people from Washington state an air sampler that simulates breathing to wear during a normal day: office work, commuting, hanging out at home. They tested for a suite of the new generation of chlorinated flame retardants and found all 10 were breathing some amount of them throughout the day.

Exposure to one of the most prevalent compounds was up to 30 times greater than ingesting the chemicals via dust. The distinction is important: dust exposure occurs largely through the mouth, previously thought to be the major exposure route for banned PBDEs.

“With PBDEs, inhalation wasn’t considered as important,” Inhalation of PBDEs accounted for between 10 and 20 percent of exposure, “With the replacements, we see quite a different picture.”

said Amina Salamova, an environmental chemist and researcher at Indiana University Bloomington who studies toxic pollutants.

Chlorinated flame retardants are used mostly in polyurethane foam, often in building insulation and everyday products such as furniture, children’s car seats and baby strollers. The compounds are substitutes for PBDEs, which were widely used as flame retardants until scientists reported they were building up in people and wildlife and various bans took hold.

The American Chemistry Council, which represents chemical manufacturers, has long maintained flame retardant chemicals are necessary to prevent fires and protect people. In response to the recent study, Bryan Goodman, director of product communications for the council, said in an email that

exposure via ingestion and inhalation is “anticipated and regulators generally take this into account” when assessing the risk of chemicals.

However, Salamova, who was not involved in the recent study, said the inhalation concerns raised by Schreder’s study were especially alarming and novel because it was levels of really small particles that were quite high. She said:

“These really go all the way down your air tract and penetrate into the lung tissue,”

While chlorinated flame retardants have been around for decades, Salamova said scientists have recently started to understand them as, at first, it was thought they weren’t harmful or able to accumulate in people and wildlife. However there is evidence the replacement are following the same path as PBDEs: chlorinated flame retardants have been found in household dust, children’s products, drinking water, and mother-toddlers pairs.

Two chlorinated flame retardants have been flagged by the state of California as carcinogens, and animal research suggests they may hamper brain development as well.

Washington state legislators introduced bills in the state House and Senate to ban five flame retardants from furniture and children’s products, which would also set up a system to make sure new replacements are safe. The bill includes flame retardants found in the air in the recent study. The House bill will have a hearing this Wednesday.

Erika Schreder, study lead author, said:

The study doesn’t give us the final answer on exposure, but it does offer “a good indication of the range” that people are exposed to.

For questions or feedback about this piece, contact Brian Bienkowski.

Chemicals in food contact materials: CHEMtrust Policy Briefing

A gap in the internal market, a failure in public protection

image of food-packaging
CHEMtrust intend to update their briefing as this policy area develops. Food packaging via hypescience.

CHEMtrust briefing “Chemicals in food contact materials: A gap in the internal market, a failure in public protection“, first published on 26th January 2016, outlines the key problems, and proposes some solutions.

Food packaging, factory equipment, food utensils – almost everything we eat has been in contact with one or more of these items. The EU’s laws should ensure that chemicals used in these materials are safe, but they do not go far enough and contain holes.

These holes – for example a lack of harmonised rules on paper and card, inks, coatings and adhesives – mean that public health is not properly protected, and also lead to disruption of the internal market.

Reanalysis of Study 329: efficacy and harms of paroxetine and imipramine in adolescents

How difficult it is to get the truth about questionable drugs

The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.

Access to primary data from trials has important implications for both clinical practice and research, including that published conclusions about efficacy and safety should not be read as authoritative.

Jon Jueridini and colleagues have reanalysed SmithKline Beecham’ infamous Study 329 (published by Keller and colleagues in 2001), the primary objective of which was to compare the efficacy and safety of paroxetine and imipramine with placebo in the treatment of adolescents with unipolar major depression.

The reanalysis under the restoring invisible and abandoned trials (RIAT) initiative was done to see whether access to and reanalysis of a full dataset from a randomised controlled trial would have clinically relevant implications for evidence based medicine.

Their analysis finds that neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs.

More on Study 329 from The BMJ
  • Study 329, doi.org/10.1136/bmj.h4973, 17 September 2015.
  • Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence, doi.org/10.1136/bmj.h4320, 16 September 2015.
  • No correction, no retraction, no apology, no comment: paroxetine trial reanalysis raises questions about institutional responsibility, doi.org/10.1136/bmj.h4629, 16 September 2015.
  • Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence, doi.org/10.1136/bmj.h4320, 16 September 2015.
  • Restoring invisible and abandoned trials: a call for people to publish the findings, doi.org/10.1136/bmj.f2865, June 28, 2013.
More on Study 329 from Dr David Healy’s blog
More on Study 329
  • Initial – 1st – Study 329, jaacap, July 2001.
  • Restoring Study 329, website.
  • About : Documenting Seroxat : An Epic Medical Scandal, truthman30/.