Discover your Dose of Nature

Nature Rx Part 2

Video published on 19 Nov 2015
by Nature Rx

Ask your doctor if nature is right for you and discover what your preferred dose of nature is.

More info and videos
  • Behind the humor and parody of Nature Rx is good science. Research shows that spending more time in nature improves your health, wellbeing, and leads to making better environmental decisions.
  • Find out more: research and wild.
  • Find more parodies videos on our YT channel.

Study 329 Lessons: published conclusions about drugs efficacy and safety should not be read as authoritative

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

study-329 poster
Unpublished and misreported studies make it difficult to determine the true value of a treatment. RIAT stands for “restoring invisible and abandoned trials.

2015 (2nd) Study Abstract

The RIAT re-analysis marks a new chapter in the story of Study 329, showing the remarkable power of open data. But it also shows how much our current systems are failing patients and the public. It should not have taken 14 years to get to this point. It shows that we need regulation, and perhaps legislation, to ensure that the results of all clinical trials are made publicly available and that individual patient data are available for legitimate independent third party scrutiny.

Objectives
To reanalyse SmithKline Beecham’s 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.

Design
Double blind randomised placebo controlled trial.

Setting
12 North American academic psychiatry centres, from 20 April 1994 to 15 February 1998.

Participants
275 adolescents with major depression of at least eight weeks in duration. Exclusion criteria included a range of comorbid psychiatric and medical disorders and suicidality.

Interventions
Participants were randomised to eight weeks double blind treatment with paroxetine (20-40 mg), imipramine (200-300 mg), or placebo.

Main outcome measures
The prespecified primary efficacy variables were change from baseline to the end of the eight week acute treatment phase in total Hamilton depression scale (HAM-D) score and the proportion of responders (HAM-D score ≤8 or ≥50% reduction in baseline HAM-D) at acute endpoint. Prespecified secondary outcomes were changes from baseline to endpoint in depression items in K-SADS-L, clinical global impression, autonomous functioning checklist, self-perception profile, and sickness impact scale; predictors of response; and number of patients who relapse during the maintenance phase. Adverse experiences were to be compared primarily by using descriptive statistics. No coding dictionary was prespecified.

Results
The efficacy of paroxetine and imipramine was not statistically or clinically significantly different from placebo for any prespecified primary or secondary efficacy outcome. HAM-D scores decreased by 10.7 (least squares mean) (95% confidence interval 9.1 to 12.3), 9.0 (7.4 to 10.5), and 9.1 (7.5 to 10.7) points, respectively, for the paroxetine, imipramine and placebo groups (P=0.20). There were clinically significant increases in harms, including suicidal ideation and behaviour and other serious adverse events in the paroxetine group and cardiovascular problems in the imipramine group.

Conclusions
Neither paroxetine nor high dose imipramine showed efficacy for major depression in adolescents, and there was an increase in harms with both drugs. 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. The reanalysis of Study 329 illustrates the necessity of making primary trial data and protocols available to increase the rigour of the evidence base.

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/.

Epigenetics: a Historical Overview

In the first half of the twentieth century, developmental biology and genetics were separate disciplines

image of epigenetics
The nature of the continual interactions between proteins and DNA will further advance the field of epigenetics, and illuminate current problems, such as the re-programming of the genome which initiates the normal processes of development.

ABSTRACT

Epigenetics attempts to provide new insights into the mechanisms for unfolding the genetic program for development.

The word epigenetics was coined by Waddington to link developmental biology and genetics. Epigenetics could be broadly defined as the sum of all those mechanisms necessary for the unfolding of the genetic programme for development. Several decades later specific mechanisms were proposed in which information was superimposed on DNA sequences. In particular, it was suggested that 5-methyl cytosine had a role in controlling gene expression, and also that the pattern of methylation was heritable. These predictions are now supported by a large body of evidence which shows that methylation is strongly associated with gene silencing in a variety of biological contexts. There are now also many examples of epigenetic inheritance through the germ line There are several other important epigenetic mechanisms involving chromatin and histone modifications, and also the expanding field of regulatory RNAs. The human epigenome project will unravel the pattern of DNA methylation in different tissues, and will this determine whether the regulation of gene expression is at the level of DNA or chromatin, or both.

Call for transnational proposals on Antimicrobial Resistance to be online soon

Joint Programming Initiative on Antimicrobial Resistance

This initiative aims to promote international research on antimicrobial resistance. The call is scheduled to open on January 18, 2016.
The JPIAMR initiative aims to promote international research on antimicrobial resistance. The call is scheduled to open on January 18, 2016.

The French National Research Agency, in partnership with 12 European countries (Belgium, Denmark, Germany, Italy, Latvia, Netherlands, Norway, Poland, Portugal, Spain, Sweden and UK), 3 associated countries (Israel, Turkey and Switzerland) and Canada, is set to launch a third joint call for proposals through the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR).

The French National Research Agency Preannouncement
An organism develops resistance to a drug either by a gene mutation or by the acquisition of genetic components from another strain (i.e. transmission of resistance). Resistant organisms can multiply in the presence of a drug (i.e. selection of resistance traits) but without transmission, resistance would remain an isolated problem.
To understand the complex biological and environmental interactions that shape the spread of antibiotic resistance, we must identify and characterise the determinants that contribute to the spread of resistance in and between different reservoirs; including humans (sick and healthy people), animals (livestock, companion and wild animals) and the environment (indoor and outdoor).

Responding collectively through research
Research in biology and epidemiology on resistance selection and transmission is therefore crucial for defining preventive measures to address this public threat. The existence and proliferation of antibiotic resistance in bacterial strains with a major impact on public health must be handled using risk analysis approaches based on bacterial pathogens’ genetic reservoirs and the environmental parameters which determine their community, veterinary, and clinical survival.
In this context, the Joint Programming Initiative on Antimicrobial Resistance aims to coordinate research efforts on these issues at the international level.

A new call for proposals planned for January
This third call for proposals will bring together the following funding organisations: FRS-FNRS and FWO (Belgium), CIHR (Canada), IFD (Denmark), BMBF/DLR (Germany), CSO-MOH (Israël), IT-MOH (Italy), VIAA (Latvia), ZonMw (Netherlands), RCN (Norway), NCN (Poland), FCT (Portugal), ICSIII and MINECO (Spain), SRC and Formas (Sweden), SNCF (Switzerland), Tubitak (Turkey) and MRC (UK).
The initiative sets out to support research aimed at unravelling the dynamics of transmission and selection of antimicrobial resistance (AMR) at genetic, bacterial, animal, human, societal, and environmental levels, in order to design and evaluate preventive and intervening measures for controlling resistance.
The primary aim of the call is to combine the resources, infrastructures, and research strengths of multiple countries in order to address transmission of antibiotic resistance following a ‘One Health Approach’.

Designed with multidisciplinary and transnational consortia in mind
The goal is to foster multinational research collaborations to add value to and to build upon the research conducted independently at national level and to work together to improve the control of resistant bacterial infections of clinical and/or veterinary importance only.
We expect that most collaborations to be multidisciplinary with expertise that could include, but are not limited to, bacteriologists (clinical, veterinary, and environmental), chemists, ecologists, mathematicians, informatics and computational modelers, medical practitioners (human and veterinary), etc., where appropriate. Consortia are encouraged to include participants from academia, medical and public health practitioners (both human and veterinary), policy makers, and industry, where appropriate (please note the national/regional regulations).