What do we do when Antibiotics do not work anymore?

TED Talks video with Maryn McKenna on Antibiotic Resistance

Penicillin changed everything. Infections that had previously killed were suddenly quickly curable. Yet as Maryn McKenna shares in this sobering talk, we’ve squandered the advantages afforded us by that and later antibiotics. Drug-resistant bacteria mean we’re entering a post-antibiotic world — and it won’t be pretty. There are, however, things we can do … if we start right now.

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I would not operate without Stilbosol in our feed

DES advert, FFA National Future Farmer, 1957

stilbosol 1957 poster
Stilbosol patenting turned the cattle feed industry upside down in the mid fifties with its phenomenal use by the farmers.
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Women who experienced a stillbirth almost five times more likely to suffer same tragedy again

Risk of recurrent stillbirth: systematic review and meta-analysis

Women who experience a stillbirth in their initial pregnancy have a higher risk of stillbirth in a subsequent pregnancy. Even after adjusting for potential confounding factors, the increased risk remains. Risk of recurrent unexplained stillbirth is largely unstudied,  evidence about this remains controversial. Roman Soto image.

2015 Study Abstract

Objective
To determine the risk of recurrent stillbirth.

Design
Systematic review and meta-analysis of cohort and case-control studies.

Data sources
Embase, Medline, Cochrane Library, PubMed, CINAHL, and Scopus searched systematically with no restrictions on date, publication, or language to identify relevant studies. Supplementary efforts included searching relevant internet resources as well as hand searching the reference lists of included studies. Where published information was unclear or inadequate, corresponding authors were contacted for more information.

Study selection
Cohort and case-control studies from high income countries were potentially eligible if they investigated the association between stillbirth in an initial pregnancy and risk of stillbirth in a subsequent pregnancy. Stillbirth was defined as fetal death occurring at more than 20 weeks’ gestation or a birth weight of at least 400 g. Two reviewers independently screened titles to identify eligible studies based on inclusion and exclusion criteria agreed a priori, extracted data, and assessed the methodological quality using scoring criteria from the critical appraisal skills programme. Random effects meta-analyses were used to combine the results of the included studies. Subgroup analysis was performed on studies that examined unexplained stillbirth.

Results
13 cohort studies and three case-control studies met the inclusion criteria and were included in the meta-analysis. Data were available on 3 412 079 women with pregnancies beyond 20 weeks duration, of who 3 387 538 (99.3%) had had a previous live birth and 24 541 (0.7%) a stillbirth. A total of 14 283 stillbirths occurred in subsequent pregnancies, 606/24 541 (2.5%) in women with a history of stillbirth and 13 677/3 387 538 (0.4%) among women with no such history (pooled odds ratio 4.83, 95% confidence interval 3.77 to 6.18). 12 studies specifically assessed the risk of stillbirth in second pregnancies. Compared with women who had a live birth in their first pregnancy, those who experienced a stillbirth were almost five times more likely to experience a stillbirth in their second pregnancy (odds ratio 4.77, 95% confidence interval 3.70 to 6.15). The pooled odds ratio using the adjusted effect measures from the primary studies was 3.38 (95% confidence interval 2.61 to 4.38). Four studies examined the risk of recurrent unexplained stillbirth. Methodological differences between these studies precluded pooling the results.

Conclusions
The risk of stillbirth in subsequent pregnancies is higher in women who experience a stillbirth in their first pregnancy. This increased risk remained after adjusted analysis. Evidence surrounding the recurrence risk of unexplained stillbirth remains controversial.

Sources and more information
  • Risk of recurrent stillbirth: systematic review and meta-analysis, thebmj, 2015;350:h3080, 24 June 2015.
  • Women with history of stillbirth at ‘high risk of another’, NHS News, June 26 2015.

Clinical trials explained

Clinical studies are designed to answer specific scientific questions

Clinical trials are essential to providing the scientific data to determine whether new drugs, diagnostics or procedures are both safe and effective when used to diagnose and treat people. Roche video, published on 28 May 2014, part of  Drawn to Science series.

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  • Carefully conducted clinical trials are performed in human volunteers to provide answers to important questions. Every new treatment is usually tested in three phases of clinical trials before regulatory agencies consider it safe and effective. Depending on product type and development stage, investigators initially enroll volunteers and/or patients into small pilot studies and subsequently conduct progressively larger scale comparative studies. As positive safety and efficacy data are gathered, the number of patients typically increases. Clinical trials can vary in size, and can involve a single research entity in one country or multiple entities in multiple countries.
  • Watch more research videos on our YouTube channel.

The Flibanserin Effect… a Cartoon by Ted Rall

Flibanserin: female love drug leaves a lot to be desired…

Flibanserin-cartoon
Ted Rall on… Viagra for women. Published: 04 June 2015 @anewdomain

The FDA is about to approve Flibanserin, marketed as the “Viagra for women” who want to increase their libidos. But according to reports, the effects aren’t dazzling. And there are some rather significant side effects…

Everyday chemicals in combination may cause cancer

Global taskforce calls for research into everyday chemicals that may cause cancer

Chemical-Attack
Fifty chemicals the public are exposed to on a daily basis may trigger cancer when combined, according to new research. Chemical Attack image by Surian Soosay.

2015 Study Abstract

Lifestyle factors are responsible for a considerable portion of cancer incidence worldwide, but credible estimates from the World Health Organization and the International Agency for Research on Cancer (IARC) suggest that the fraction of cancers attributable to toxic environmental exposures is between 7% and 19%.

To explore the hypothesis that low-dose exposures to mixtures of chemicals in the environment may be combining to contribute to environmental carcinogenesis, we reviewed 11 hallmark phenotypes of cancer, multiple priority target sites for disruption in each area and prototypical chemical disruptors for all targets, this included dose-response characterizations, evidence of low-dose effects and cross-hallmark effects for all targets and chemicals.

In total, 85 examples of chemicals were reviewed for actions on key pathways/mechanisms related to carcinogenesis. Only 15% (13/85) were found to have evidence of a dose-response threshold, whereas 59% (50/85) exerted low-dose effects. No dose-response information was found for the remaining 26% (22/85).

Our analysis suggests that the cumulative effects of individual (non-carcinogenic) chemicals acting on different pathways, and a variety of related systems, organs, tissues and cells could plausibly conspire to produce carcinogenic synergies. Additional basic research on carcinogenesis and research focused on low-dose effects of chemical mixtures needs to be rigorously pursued before the merits of this hypothesis can be further advanced. However, the structure of the World Health Organization International Programme on Chemical Safety ‘Mode of Action’ framework should be revisited as it has inherent weaknesses that are not fully aligned with our current understanding of cancer biology.

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Transplantation utérine: des greffes d’utérus vont être tentées en France

La transplantation utérine ; une alternative aux mères porteuses?

image de femme-regardant-la-mer
Mardi 23 juin, l’Académie nationale de médecine a adopté un rapport sur la transplantation utérine. Image Markus M.
Résumé

Après avoir fait le récit des événements qui ont précédé la première transplantation utérine ayant abouti à la naissance d’un enfant vivant et bien portant et fait un état des lieux, les auteurs exposent la législation française actuelle sur la greffe d’organes. Puis, ils abordent les aspects cliniques, insistant sur la complexité de l’acte chirurgical, le dilemme du choix entre donneuse en état de mort cérébrale ou décédée et donneuse vivante, et les indications chez la receveuse. Ils décrivent ensuite le traitement immunosuppresseur avant et pendant la grossesse, les complications plus ou moins graves qui peuvent en émailler le cours et la surveillance particulièrement attentive qu’elles nécessitent, mais aussi les doutes sur l’opportunité de l’allaitement maternel. Ils s’interrogent sur l’avenir de l’enfant à moyen et long terme, son développement psychomoteur et celui de son système immunitaire. Ils retracent les nombreuses et délicates questions éthiques que pose la transplantation utérine, qu’il s’agisse des particularités de la greffe d’utérus, qui n’est pas vitale mais permet de donner la vie, du choix entre transplantation avec donneuse en état de mort cérébrale ou donneuse vivante, de la pénurie d’organes à greffer, des risques courus par la receveuse, du devenir physique et psychologique de l’enfant, enfin du choix entre transplantation utérine et gestation pour autrui et de l’éventualité de dérives. En fait, la transplantation utérine est une chirurgie encore au stade expérimental et seuls l’avenir et le recueil exhaustif de toutes les données la concernant permettront de s’assurer de son bien fondé.

En savoir plus
  • La transplantation utérine, Académie nationale de médecine, rapport du 23 juin 2015.
  • Des greffes d’utérus vont être tentées en France. C’est une alternative aux mères porteuses, jeanyvesnau, 2015/06/24.

I never had daily gains like these heifers gave me

Stilbosol patenting turned the cattle feed industry upside down in the mid fifties with its phenomenal use by the farmers and feeders

stilbosol-ad-1957
FFA National Future Farmer, IUPUI archives.
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Low-dose exposures to chemical mixtures in the environment and cancer risk

Low-Dose Exposures to Chemical Mixtures in the Environment linked to Human Cancer: Cause and Prevention

The relative contribution of the environment, genetic susceptibility and DNA replication errors to cancer causation has been a longstanding area of investigation in the fields of molecular epidemiology of cancer and carcinogenesis.

Low-dose exposures to common environmental chemicals that are deemed safe individually may be combining to instigate carcinogenesis, thereby contributing to the incidence of cancer. This risk may be overlooked by current regulatory practices and needs to be vigorously investigated.

Carcinogenesis published a series of reviews on the carcinogenic potential of exposure to low doses and mixtures of chemicals.

  • Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression, Suppl_1/S2.full, September 19, 2014.
  • Disruptive chemicals, senescence and immortality, Suppl_1/S19.full, August 5, 2014.
  • The potential for chemical mixtures from the environment to enable the cancer hallmark of sustained proliferative signalling, Suppl_1/S38.full, December 15, 2014.
  • Causes of genome instability: the effect of low dose chemical exposures in modern society, Suppl_1/S61.full, December 11, 2014.
  • Disruptive environmental chemicals and cellular mechanisms that confer resistance to cell death, Suppl_1/S89.full, February 3, 2015.
  • Chemical compounds from anthropogenic environment and immune evasion mechanisms: potential interactions, Suppl_1/S111.full, January 19, 2015.
  • The impact of low-dose carcinogens and environmental disruptors on tissue invasion and metastasis, Suppl_1/S128.full, November 19, 2014.
  • The effect of environmental chemicals on the tumor microenvironment, Suppl_1/S160.full, November 28, 2014.
  • Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis, Suppl_1/S184.full, December 15, 2014.
  • Metabolic reprogramming and dysregulated metabolism: cause, consequence and/or enabler of environmental carcinogenesis?, Suppl_1/S203.full, February 24, 2015.
  • Environmental immune disruptors, inflammation and cancer risk, Suppl_1/S232.full, January 14, 2015.
  • Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: the challenge ahead, Suppl_1/S254.full, January 31, 2015.

Will medical care and public health be radically transformed by precision, personalized medicine?

Seven Questions for Personalized Medicine

Companion diagnostics lab image
Will medical care and public health be radically transformed by prevention and treatment programs more closely targeted to the individual patient? Companion diagnostics lab image by QIAGEN.

Personalized or precision medicine maintains that medical care and public health will be radically transformed by prevention and treatment programs more closely targeted to the individual patient. These interventions will be developed by sequencing more genomes, creating bigger biobanks, and linking biological information to health data in electronic medical records (EMRs) or obtained by monitoring technologies. Yet the assumptions underpinning personalized medicine have largely escaped questioning.

The Journal of the American Medical Association stimulate a more balanced debate by posing seven questions for the advocates of personalized medicine:

  1. DOES THE HUMAN GENOME CONTRIBUTE TO DISEASE RISK PREDICTION?
  2. WILL GENE-BASED DRUG TARGETING AND DEVELOPMENT FULFILL ITS PROMISE?
  3. WHAT WILL EMRS CONTRIBUTE?
  4. WHAT KINDS OF STUDIES SHOULD BE MOUNTED IN PERSONALIZED MEDICINE?
  5. HOW SHOULD INSTITUTIONAL CONFLICTS OF INTEREST BE MANAGED IN PERSONALIZED MEDICINE?
  6. HOW WILL PERSONALIZED MEDICINE AFFECT THE COSTS OF MEDICAL CARE?
  7. WHERE IS THE PUBLIC HEALTH BENEFIT?

Read Seven Questions for Personalized Medicine,
JAMA, doi:10.1001/jama.2015.7725, Published online June 22, 2015.