Communicating the Harmful Effects of Medicines – May Warnings have unintended Consequences?

Did suicide warnings around antidepressants cause more suicide?

Abstract

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Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people.

Objective
To investigate if the widely publicized warnings in 2003 from the US Food and Drug Administration about a possible increased risk of suicidality with antidepressant use in young people were associated with changes in antidepressant use, suicide attempts, and completed suicides among young people.

Design
Quasi-experimental study assessing changes in outcomes after the warnings, controlling for pre-existing trends.

Setting
Automated healthcare claims data (2000-10) derived from the virtual data warehouse of 11 health plans in the US Mental Health Research Network.

Participants
Study cohorts included adolescents (around 1.1 million), young adults (around 1.4 million), and adults (around 5 million).

Main outcome measures
Rates of antidepressant dispensings, psychotropic drug poisonings (a validated proxy for suicide attempts), and completed suicides.

Results
Trends in antidepressant use and poisonings changed abruptly after the warnings. In the second year after the warnings, relative changes in antidepressant use were −31.0% (95% confidence interval −33.0% to −29.0%) among adolescents, −24.3% (−25.4% to −23.2%) among young adults, and −14.5% (−16.0% to −12.9%) among adults. These reflected absolute reductions of 696, 1216, and 1621 dispensings per 100 000 people among adolescents, young adults, and adults, respectively. Simultaneously, there were significant, relative increases in psychotropic drug poisonings in adolescents (21.7%, 95% confidence interval 4.9% to 38.5%) and young adults (33.7%, 26.9% to 40.4%) but not among adults (5.2%, −6.5% to 16.9%). These reflected absolute increases of 2 and 4 poisonings per 100 000 people among adolescents and young adults, respectively (approximately 77 additional poisonings in our cohort of 2.5 million young people). Completed suicides did not change for any age group.

Conclusions
Safety warnings about antidepressants and widespread media coverage decreased antidepressant use, and there were simultaneous increases in suicide attempts among young people. It is essential to monitor and reduce possible unintended consequences of FDA warnings and media reporting.

Sources
  • Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study, BMJ 2014;348:g3596, 18 June 2014.
  • Communicating the harmful effects of medicines,
    BMJ 2014; 348 bmj.g4047, 18 June 2014.
  • Did suicide warnings around antidepressants cause more suicide?
    a tweet from Ben Goldacre.

EDCs – Reproductive and Fertility Problems, including Low Sperm Count

This post is part of our new “EDCs HEAL serie“

Reproductive and fertility problems, including low sperm count

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The rate at which couples are seeking medical assistance due to infertility is increasing at more than 10% per year

By 1992, sperm quality across the European population was reported to have declined by 50% in the previous 50 years. A recent study of 26,600 men in France showed sperm count had fallen by a third between 1989 and 2005. Furthermore, a Spanish study found that even in young men, sperm concentration was falling by an average of two percent a year.

An estimated one in six couples seeks help in conceiving a child. The demand for treatment in Europe – as expressed in treatment cycles performed in European countries – has increased by 59% in the five years.

Sources – @HealthandEnv HEAL News

Powerful Mix of AntiPsychotics and Sedatives routinely prescribed to Seniors in Nursing Homes

Antipsychotics and sedatives drugs are prescribed commonly because they are perceived to be benign – while they are inherently dangerous

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Antipsychotics and sedatives drugs are prescribed commonly because they are perceived to be benign – while they are inherently dangerous.

Thousands of seniors in Ontario nursing homes are on a powerful mix of antipsychotics and sedatives, according to a new provincial Health Ministry report that surfaced after a recent Torstar News Service investigation.

The report, commissioned by the ministry and co-authored by a leading doctor and scientist, sheds new light on the widespread use of powerful prescription drugs among the vulnerable elderly. ‘

Read ‘Inherently dangerous’ drugs routinely prescribed to seniors: Report, MetroNews.ca, April 21, 2014

The Effect of DiEthylStilbestrol DES on Male Offspring

Genital tract abnormalities that are both structural and functional are common in DES-exposed males

image of PubMed NCBI The Endocrine Society logo
Administration of DiEthylStilbestrol DES during pregnancy appears to be followed by male genital tract abnormalities that are both structural and functional.

Various complications of pregnancy, notably threatened abortion, were commonly treated with diethylstilboestrol (DES) during the 1940’s through the 1960’s. Prenatal exposure to DES became a cause for concern in 1971 when accumulated evidence linked clear-cell adenocarcinoma of the vagina and vaginal adenosis with the administration of DES during pregnancy to the mothers of the affected young women.

Later, concern arose regarding hazards of transplacental DES on the developing male fetusFollow-up comparison 25 years or later on subjects involved in a double-blind study of the efficacy of DES in preventing untoward effects of pregnancy showed DES-exposed males to have a greater prevalence of epididymal cysts, hypoplastic testes or both. Of 308 males exposed to DES, 31.5 percent had epididymal cysts, hypoplastic testes or both, as compared with 7.8 percent of 307 placebo-exposed controls. Of 26 DES-exposed males with testicular hypoplasia, 17 had a history of cryptorchidism, while only 1 of 6 placebo-exposed males with testicular hypoplasia had a history of testicular maldescent. Analysis of semen of 134 males exposed to DES showed severe pathologic changes in 18 percent compared with 8 percent of 87 male controls. This finding suggests that DES exposure in utero may have an effect on male fertility.

Although there is no control study showing an increased incidence of malignant tumors among DES-exposed men,one must keep in mind the increased risk of testicular carcinoma in testes that are or were cryptorchid. Testicular carcinoma has been reported in three men who had a history of exposure to DES in utero and of cryptorchidism. There has as yet been no report of carcinoma of the prostatic utricle in men exposed to DES in utero. The prostatic utricle, the miillerian duct remnant that is homologous to the female vagina, has been found to be the site of carcinoma in older men.

In summary, administration of DES during pregnancy appears to be followed by male genital tract abnormalities that are both structural (epididymal cysts, hypoplastic testes and cryptorchidism) and functional (abnormal semen). Due to prolonged latency in expression of DES effects, it will probably be another decade or more before the question of potential malignancy in men exposed to DES in utero is answered. Additional follow-up will also give insight into the probability of sub-normal fertility in males exposed to DES in utero.

THE WESTERN JOURNAL OF MEDICINE, EPITOMES-PEDIATRICS, ROBERT PENNY MD, APRIL 1982

Sources:
  • Pediatrics-epitomes of progress: the effect of des on male offspringNCBI, PMID 18749074 PMCID: PMC1273720,
    West J Med. 1982 Apr;136(4):329-30.
More DES DiEthylStilbestrol Resources

EDCs – Endocrine Disruptors may cause up to €31 Billion per Year in Health Costs in the EU

This post is part of our new “EDCs HEAL serie“

€31 billion per year in EU health savings possible from reducing exposures to hormone disrupting chemicals

Health and Environment logo
HEAL is a leading alliance of health and environment groups working at EU level. Working for better health, through a healthy environment.

Exposure to food and everyday electronic, cosmetic and plastic products containing endocrine disrupting chemicals (EDCs) may be costing up to €31 billion per year in the EU, according to a report launched today by the HEAL.

  • Spiralling rates of hormone-related disease may be due to exposure to hormone-mimicking synthetic chemicals found in food, drink and everyday products.
  • New study says if a small portion of hormone-related cancers, diabetes & obesity, and infertility could be avoided by reducing exposure to hormone disrupting chemicals, then billions in costs from these diseases and conditions could be saved.
  • A change in European chemicals policy could massively reduce costs associated with cases of hormone-related diseases and conditions. EU should act now.

Sources – @HealthandEnv HEAL News

  • Health costs in the EU – How much is related to EDCs?
    Latest news and Full Report, 18 June 2014.
  • EU health savings up to €31 billion per year possible from reducing EDC exposuresPress Release, 18 June 2014.

Sounding The Alarm, Video Trailer

Documentary which examines the lives of 12 families who live with autism, and chronicles the challenges and opportunities they face from diagnosis to adulthood

Sounding the Alarm is a documentary which examines the lives of 12 families who live with autism, and chronicles the challenges and opportunities they face from diagnosis to adulthood.

More information

You will meet Too much False Precision…

Hilda Bastian is cartoonist and writer at StatisticallyFunny blog

Fortune teller - medium
Predicting the future of all groups of people – based on what happened to another group of people in the past – cannot prove precise for all individuals… a cartoon by @HildaBast

The chances of the results to be around – for ex: 62 to 73% – can be pretty slim or very high, depending on lots of things… See this chart highlighting today’s increased health risks for DES Daughters…

Hilda Bastian is Editor etc at PubMed Health, blogger at Scientific American. Commenting on epidemiology with cartoons at Statistically funny.

Read You will meet too much false precision…. by Hilda Bastian.
See more comics.

On Flickr®

Watch the Diaporama, and the health comics album on  DES Diethylstilbestrol's photostream on Flickr

If you already have a flickr® account, add us as a contact
Email your photos to des.daughter@gmail.com with a short description and title :-)

Uterine Morcellation Disseminating Unexpected Malignancy with Associated High Increase in Mortality

Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms

Abstract

PLoS logo
Uterine morcellation carries a risk of disseminating unexpected malignancy with apparent associated increase in mortality much higher than appreciated currently

Background:
Power morcellation has become a common technique for the minimally invasive resection of uterine leiomyomas. This technique is associated with dissemination of cellular material throughout the peritoneum. When morcellated uterine tumors are unexpectedly found to be leiomyosarcomas or tumors with atypical features (atypical leiomyoma, smooth muscle tumor of uncertain malignant potential), there may be significant clinical consequences. This study was undertaken to determine the frequency and clinical consequence of intraperitoneal dissemination of these neoplasms.

Methodology/Principal Findings:
From 2005-2010, 1091 instances of uterine morcellation were identified at BWH. Unexpected diagnoses of leiomyoma variants or atypical and malignant smooth muscle tumors occurred in 1.2% of cases using power morcellation for uterine masses clinically presumed to be “fibroids” over this period, including one endometrial stromal sarcoma (ESS), one cellular leiomyoma (CL), six atypical leiomyomas (AL), three smooth muscle tumor of uncertain malignant potential (STUMPs), and one leiomyosarcoma (LMS). The rate of unexpected sarcoma after the laparoscopic morcellation procedure was 0.09%, 9-fold higher than the rate currently quoted to patients during pre-procedure briefing, and this rate may increase over time as diagnostically challenging or under-sampled tumors manifest their biological potential. Furthermore, when examining follow-up laparoscopies, both from in-house and consultation cases, disseminated disease occurred in 64.3% of all tumors (zero of one ESS, one of one CL, zero of one AL, four of four STUMPs, and four of seven LMS). Only disseminated leiomyosarcoma, however, was associated with mortality. Procedures are proposed for pathologic evaluation of morcellation specimens and associated follow-up specimens.

Conclusions/Significance:
While additional study is warranted, these data suggest uterine morcellation carries a risk of disseminating unexpected malignancy with apparent associated increase in mortality much higher than appreciated currently.

Sources:
  • Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms, NCBI, PMC3506532, doi: 10.1371/journal.pone.0050058, PLoS One. 2012; 7(11): e50058., Epub 2012 Nov 26.

Many BPA-free Brands advertised as Safe while messing with Your Hormones

Estrogenic chemicals often leach from #BPA-free plastic products that are replacements for BPA-containing polycarbonate products

Abstract

BioMed Central twitter logo
Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products.

BACKGROUND:
Xenobiotic chemicals with estrogenic activity (EA), such as Bisphenol-A (BPA), have been reported to have potential adverse health effects in mammals, including humans, especially in fetal and infant stages. Concerns about safety have caused many manufacturers to use alternatives to polycarbonate (PC) resins to make hard and clear, reusable, plastic products that do not leach BPA. However, no study has focused on whether such BPA-free PC-replacement products, chosen for their perceived higher safety, especially for babies, also release other chemicals that have EA.

METHODS:
We used two, well-established, mammalian cell-based, assays (MCF-7 and BG1Luc) to assess the EA of chemicals that leached into over 1000 saline or ethanol extracts of 50 unstressed or stressed (autoclaving, microwaving, and UV radiation) BPA-free PC-replacement products. An EA antagonist, ICI 182,780, was used to confirm that agonist activity in leachates was due to chemicals that activated the mammalian estrogen receptor.

RESULTS:
Many unstressed and stressed, PC-replacement-products made from acrylic, polystyrene, polyethersulfone, and TritanTM resins leached chemicals with EA, including products made for use by babies. Exposure to various forms of UV radiation often increased the leaching of chemicals with EA. In contrast, some BPA-free PC-replacement products made from glycol-modified polyethylene terephthalate or cyclic olefin polymer or co-polymer resins did not release chemicals with detectable EA under any conditions tested.

CONCLUSIONS:
This hazard assessment survey showed that many BPA-free PC- replacement products still leached chemicals having significant levels of estrogenic activity, as did BPA-containing polycarbonate counterparts they were meant to replace. That is, BPA-free did not mean EA-free. However, this study also showed that some PC-replacement products did not leach chemicals having significant levels of EA. That is, EA-free PC-replacement products could be made in commercial quantities at prices that compete with PC-replacement products that were not BPA-free. Since plastic products often have advantages (price, weight, shatter-resistance, etc.) compared to other materials such as steel or glass, it is not necessary to forgo those advantages to avoid release into foodstuffs or the environment of chemicals having EA that may have potential adverse effects on our health or the health of future generations.

Sources and Press Articles
  • Estrogenic chemicals often leach from BPA-free plastic products that are replacements for BPA-containing polycarbonate products, NCBI, PMID: 24886603, 2014 May 28.
  • Full text, Environmental Health, doi:10.1186/1476-069X-13-41, 2014 May 28.
  • Parents shocked to learn ‘BPA-free’ baby bottles are loaded with other estrogen mimickers: Born Free, Weil Baby, CamelBak and more, NaturalNews, 045585_BPA-free_baby_bottles_estrogen_mimickers, June 16, 2014.
  • These Popular Plastic Bottles May Be Messing With Your Hormones, MotherJones, bpa-free-plastics-tritan-nalgene-dangerous, Jun. 16, 2014.

Bisphenol A Long-Term Adverse Reproductive and Carcinogenic Effects

Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life

Abstract

ehp twitter graphic
BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.

Background:
Exposure to endocrine-disrupting chemicals during critical developmental periods causes adverse consequences later in life; an example is prenatal exposure to the pharmaceutical diethylstilbestrol (DES). Bisphenol-A (BPA), an environmental estrogen used in the synthesis of plastics, is of concern because its chemical structure resembles that of DES, and it is a “high-volume production” chemical with widespread human exposure.

Objective:
In this study we investigated whether prenatal Bisphenol-A causes long-term adverse effects in female reproductive tissues in an experimental animal model previously shown useful in studying effects of prenatal DES.

Methods:
Timed pregnant CD-1 mice were treated on days 9-16 of gestation with BPA (0.1, 1, 10, 100, or 1,000 mug/kg/day). After delivery, pups were held for 18 months; reproductive tissues were then evaluated.

Results:
Ovarian cysts were significantly increased in the 1-mug/kg BPA group; ovarian cyst-adenomas were seen in the other three BPA-treated groups but not in corn-oil controls. We observed increased progressive proliferative lesions of the oviduct after BPA treatment, similar to those described in response to DES. Further, although not statistically different from the controls, prominent mesonephric (Wolffian) remnants and squamous metaplasia of the uterus, as well as vaginal adenosis, were present in BPA-treated mice, similar to lesions reported following DES treatment. More severe pathologies observed in some BPA-treated animals included atypical hyperplasia and stromal polyps of the uterus; sarcoma of the uterine cervix; and mammary adenocarcinoma. We did not observe these lesions in controls.

Conclusion:
These data suggest that BPA causes long-term adverse reproductive and carcinogenic effects if exposure occurs during critical periods of differentiation.

Sources
  • Prenatal exposure to bisphenol a at environmentally relevant doses adversely affects the murine female reproductive tract later in life., Environ Health Perspect ; 117(6):879-85. doi: 10.1289/ehp.0800045, 19590677, 2009 Jun.
  • Full text : NCBI, PMC2702400, Jan 15, 2009.