On 2017 Aug 14, Egon Willighagen commented:

The data from Table I and II is available as machine readable HTML+RDFa from http://egonw.github.io/cheminformatics.classics/classic1.html

On 2014 Apr 01, Christopher Southan commented:

An updated (2013) comparison of public bioactive chemistry databases is available as http://www.ncbi.nlm.nih.gov/pubmed/24533037

On 2017 Apr 01, Egon Willighagen commented:

Tony, the current code uses Java applets, but these are no longer usable on modern browsers due to discontinued support. Do you have an updated approach to include spectra from ChemSpider in webpages as you describe in the paper?

On 2017 Apr 12, Antony J. Williams commented:

None

On 2014 Jan 10, Helmi BEN SAAD commented:

The third author name is "BEN SAAD H" not "SAAD HB".

On 2016 Feb 07, Fang-Cheng Yeh commented:

The tool and source code are available at http://dsi-studio.labsolver.org/

On 2014 May 10, Ivan Oransky commented:

This paper has been retracted: http://retractionwatch.com/2014/05/08/retraction-appears-for-former-federal-contractor-who-faked-data/

On 2013 Dec 28, Tsuyoshi Miyakawa commented:

The finding of elevated D2High receptors in the CaMKIIalpha heterozygous knockout mice is quite interesting, regarding the possiblity that these mice may serve as an animal model of schizophrenia or bipolar disorder. We pointed out the possibility in our paper before(Yamasaki N, 2008), though it was not cited in this paper. I'd like to add that the same KO mice also show decreased cellular activity in dentate gyrus, while it is increased in CA1 in hippocampus (Hattori S, 2013), which is also consistent with the hippocampus dysfunction hypothesis of schizophrenia (Tamminga CA, 2010).

On 2016 Jun 08, Jafar Kolahi commented:

This article has been criticized at: Kolahi J, Bang H, Park JJ, Desbiens NA. CONSORT 2010 and Controversies Regarding Assessment of Blindness in RCTs. Dent Hypotheses 2010;1:99-105. doi:10.5436/j.dehy. 2010.1.00016.

Full text is available via: https://www.researchgate.net/profile/Jafar_Kolahi/publication/49583226_CONSORT_2010_and_Controversies_Regarding_Assessment_of_Blindness_in_RCTs/links/0f2cd8bca299367d1640cfd0.pdf

On 2015 Aug 06, Carrie Price commented:

Please correct the spelling of United States so that the article can be located through keyword searching.

On 2014 Sep 03, Matthew Katz commented:

This phase III trial is a classic example of how combined modality therapy (radiation combined with medical therapy) can provide effective cure for laryngeal cancer with an organ-preserving approach that can mean a major difference in quality of life. Surgery still may be needed, but for patients with a good response chemoradiation can be an effective nonsurgical treatment. More recent studies have suggested that doing the two treatments together (concurrent therapy) is superior though the toxicity may also be higher Forastiere AA, 2003

On 2014 May 09, Madhusudana Girija Sanal commented:

It is all about numbers! It is statistics which defines what cancer is! One reason is that all definitions are a matter convenience for humans to classify, work or learn. Definitions quite often cannot be ‘black and white’ and hence statistical approaches are wise. The author note that the sixth hall mark of six hallmarks defined by Hannan and Weinberg, that is “the ability to invade and metastasis” is the only ‘real’ hallmark of cancer. However it is known that everything moves around, invade and proliferate need not be a cancer- example is endometriosis. Giant-cell tumor of the bone is considered benign but can spread to other parts including the lungs. Moreover during embryonic development different cell lineages compete and invade each other. Winners proliferate secrete autocrine factors, attracts blood vessels, force defeated cells to apoptosis or even ‘eat’ them up. This is not cancer! So what can be the hallmark or defining features of cancer? What I am proposing is a preliminary outline which may be further modified by “Wiki” efforts to make it more accurate. The following conditions needs to be satisfied to define a cancer: 1) Non physiological rate of cell division. Non physiological rate is defined as a growth rate which is a statistical outlier spatially and temporally for a given type of cell and organism. 2) A change, genetic or epigenetic with reference to the healthy genome which is a statistical outlier spatially and temporally for a given cell type and organism. Healthy reference genome and epigenome may be defined as the genome of individuals which satisfy two conditions a) falling within the statistically defined normal range of anatomical and physiological parameters for a population b) demonstrated longevity above 99.9 percentile of the population of a given organism.

Cancer is a dynamic process-continuous evolution and selection. It is often,but not mandatory (at least theoretically) to be started by or seeded by a mutation and 'nurtured' or maintained by epigenetics. This is because epigenetic modification are faster as well as reversible. The effect of environment is mediated often (through cytokines, microRNA or even by physical factors) through epigenetic adaptations.Sooner or later more mutations and epigenetic changes accumulate during evolution and selection. This process is accelerated by chemotherapy (especially when using alkylating agents) radiation. Very specific and interesting mutations can evolve during targeted therapy (example-nilotinib).

On 2014 Feb 13, David Keller commented:

The April 2010 Resident's Clinic discussed a 38-year-old woman with a history of gastric bypass who presented with profound anemia due to severe copper deficiency. She was noted to have an abnormally high zinc level. Her copper deficiency was attributed mainly to malabsorption due to her bowel surgery, and it was also noted that high zinc levels may induce copper deficiency. The question then arises as to why her zinc level was so high. The only clue is that the patient "had a history of frequent upper respiratory infections". Unfortunately, she was not asked whether she had used any of the over-the-counter zinc lozenge products which are sold as alternative sore throat remedies (for example "Cold-Eze"). Clinicians should not neglect to inquire about such non-prescription remedies or supplements when taking a patient's medication history, as important information may be learned.

On 2014 Sep 06, Ryan Radecki commented:

Post-publication commentary: "The Most Dangerous Holiday!"

Here in the United States, it is Labor Day – a Federal holiday established in 1886 by U.S. President Grover Cleveland. We, apparently, have Canada to thank for this innovation.

But, what was actually news to me – Labor Day is actually the highest-volume holiday for pediatric trauma, outpacing all other holidays. I’d have thought 4th of July – with it’s various explosive devices – would be the most popular pediatric trauma holiday, but, between 1997 and 2006, Labor Day takes the lead, followed by Memorial Day, and 4th of July as a close third. Halloween, Easter, Thanksgiving, New Year’s and Christmas round out the list, in that order.

http://www.emlitofnote.com/2014/09/the-most-dangerous-holiday.html

On 2017 Aug 05, Fernando Castro-Chavez commented:

Dear Reader, Here is where I did the discovery for the first time that by using the rotating circular classic representation of the genetic code, a series of resonances were able to be found, such as that every 90 degrees we had the hydrophobic amino acids per each quadrant, and the same applies when studying the rest of the properties of the amino acids, there is resonance for the basic, and for the hydrophobic amino acids, as well as for the phosphorilatable ones. This lead me to discover the rules of variation, that equivalent amino acids, produced by equivalent codons allow for the equally functional diversity of proteins and enzymes making all the wonderful array of varieties within each group of compatible organisms, which are the ones capable to interbreed producing a fertile offspring. Sincerely, Fernando Castro-Chavez.

On 2017 Jan 20, Andy Collings commented:

A subset of experimental results from this study were the focus of a replication attempt as part of the Reproducibility Project: Cancer Biology (https://osf.io/e81xl/wiki/home/). The experimental designs and protocols were reviewed and approved in a Registered Report (http://dx.doi.org/10.7554/eLife.06959) and the results of the experiments were published in a Replication Study (http://dx.doi.org/10.7554/eLife.17584).

On 2016 Nov 18, Morten Oksvold commented:

An investigation committee at Wayne State University (WSU) recommends that 42 articles from Fazlul Sarkar to be retracted (report finished August 31, 2015). This article represents one of them.

This information was published by Retraction Watch (November 17, 2016) and you can find a link to the full report here:

http://retractionwatch.com/2016/11/17/details-of-investigative-report-into-sarkar-released-by-aclu/

This article should therefore no longer be cited.

On 2017 Apr 23, Md. Shahidul Islam commented:

In human beta cells TRPM5 is almost absent while its closest relative TRPM4 is abundant. Marabita F, and Islam MS. Pancreas. 2017 Jan;46(1):97-101. Expression of Transient Receptor Potential Channels in the Purified Human Pancreatic β-Cells. PMID: 27464700 DOI: 10.1097/MPA.0000000000000685

On 2016 Aug 24, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00018255. We believe the correct ID, which we have found by hand searching, is NCT01068210.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2014 Jun 01, Ivan Oransky commented:

This paper has been retracted: http://retractionwatch.com/2014/05/28/failure-to-cite-leads-to-ignoble-end-for-xenon-paper-and-a-correction/

On 2013 Dec 31, Tom Kindlon commented:

I had a response published: FINE trial for CFS. Missing data

BMJ. 2010 Jun 9;340:c2990. doi: 10.1136/bmj.c2990. FINE trial for CFS. Missing data. Kindlon T. http://www.ncbi.nlm.nih.gov/pubmed/20534661 Kindlon T, 2010

My original e-letter from which this was drawn can be read here: http://www.bmj.com/rapid-response/2011/11/02/missing-data

On 2015 Dec 24, Tom Kindlon commented:

Step test data were subsequently published

"There were no between group differences in any of the step test measures at 20 or 70 weeks"(1).

Reference:

Wearden AJ1, Emsley R. Mediators of the effects on fatigue of pragmatic rehabilitation for chronic fatigue syndrome. J Consult Clin Psychol. 2013 Oct;81(5):831-8. doi: 10.1037/a0033561.

On 2016 Nov 20, Morten Oksvold commented:

An investigation committee at Wayne State University (WSU) recommends that 42 articles from Fazlul Sarkar to be retracted (report finished August 31, 2015). This article represents one of them.

This information was published by Retraction Watch (November 17, 2016) and you can find a link to the full report here:

http://retractionwatch.com/2016/11/17/details-of-investigative-report-into-sarkar-released-by-aclu/

This article should therefore no longer be cited.

On 2016 Mar 18, ZHONGMING ZHAO commented:

My lab recently moved to the University of Texas Health Science Center at Houston. The database is now available at https://bioinfo.uth.edu/SZGR/.

On 2014 Jul 16, Egon Willighagen commented:

The Chemistry Development Kit has an Open Source (LGPL) implementation of these fingerprints: http://cdk.sf.net/.

On 2013 Oct 28, Jamie Horder commented:

A historical note: in January 2009, shortly before this study was due to be completed, it was terminated early on the instructions of the local Research Ethics Committee. The reason for this was that rimonabant had just been withdrawn from the European market due to concerns over the high prevalence of depression in users - ironically, the very phenomenon that motivated this study.

On 2016 Sep 19, Morten Oksvold commented:

Please note that a rather extensive correction was published 7 December 2011: "The wrong images were mistakenly presented for day 3 for the wild-type and the racX ylmE double mutant in figure S4. The original and correct images are now shown. Also, the wrong image was presented for the mixture of L-amino acids in panel B of fig. S13 and has now been removed."

In 2013, the Losick group published results showing that D-amino acids inhibited bacterial growth and the expression of biofilm matrix genes and that the strain they originally used to study biofilm formation (B. subtilis) has a mutation in the D-tyrosyl-tRNA deacylase gene, an enzyme that prevents the misincorporation of D-amino acids into protein (Leiman et al., 2013). In a B. subtilis strain, which has a working copy of this gene, D–amino acids did not inhibit biofilm formation. The conclusion from their study was that "the susceptibility of B. subtilis to the biofilm-inhibitory effects of D-amino acids is largely, if not entirely, due to their toxic effects on protein synthesis.

Does that mean that they no longer see D-amino acids as a specific mechanism to disassemble biofilms in B. subtilis but rather as nonspecific inhibitors of growth in some genetic backgrounds?

Leiman et al. (2013) make no comment on the ability of D-amino acids to inhibit biofilm formation in staphylococcus aureus and Pseudomonas aeruginosa, as claimed in this article. The whole concept of biofilm dissasembly by D-amino acids therefore appears confusing.

It was recently published an article showing that D-amino acids do not inhibit biofilm formation in Staphylococcus aureus (Sarkar S and Pires MM, 2015).

On 2016 Oct 13, Ilana Kolodkin-Gal commented:

The supporting material for this paper was corrected, and the source data were provided to the editors of the Science journal. As for D-amino acids and biofilm formation: Non-canonical D-amino acids are small molecules interfering with cross-linking and transglycosylation of the peptidoglycan (Lam et al., 2009; Cava et al., 2011), and have been shown to trigger biofilm disassembly (Kolodkin-Gal et al., 2010), without affecting planktonic growth. This observation was later reproduced in various model organisms, such as Staphylococcus aureus (Hochbaum et al., 2011; Sanchez et al., 2013), Pseudomonas aeruginosa (Yu et al., 2012; Sanchez et al., 2014), the plant pathogen Xanthomonas citri (Li and Wang, 2014) , Escherichia coli (Xing et al., 2015) and in mixed biofilms (Si et al., 2014), as well as in other models published in numerous more recent publications. Furthermore, in our group we have generated so far two independent peer-reviewed publications clarifying the mode of action of D-aa for biofilm inhibition: http://onlinelibrary.wiley.com/doi/10.1111/1758-2229.12346/abstract http://www.jove.com/video/54612/methodologies-for-studying-b-subtilis-biofilms-as- Lastly, we established a consistent and robust experimental framework to study the effect of these small molecules biofilm inhibitors (Bucher et al., 2016).

On 2014 Jun 21, Ivan Oransky commented:

This paper has been retracted, the eighth retraction for the last author: http://retractionwatch.com/2014/06/17/researcher-who-tampered-with-investigation-up-to-8-retractions/

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT0027813. We believe the correct ID, which we have found by hand searching, is NCT00278135.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2015 Jan 16, Sebastien Moretti commented:

The authors state that only RevTrans does not require "the amino acid alignment together with nucleotide sequences" as input. Also ProtoGene does not. Its purpose is to back-translate amino acid alignments/sequences without nucleotide sequences, only based on protein blast similarity.

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2014 Jul 31, Sandra Porter commented:

I enjoyed the way the authors dissected the function of these proteins and posted some images and directions here Along came a spider to show how others could explore the structure.

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00122184. We believe the correct ID, which we have found by hand searching, is NCT00132184.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00527782. We believe the correct ID, which we have found by hand searching, is NCT00527787.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2013 Oct 28, John Cannell commented:

The control group in this study was flawed. The authors used children undergoing outpatient tonsillectomies as controls. Such children are likely to have low 25(OH)D levels.

Seventy-eight percent of Auckland children undergoing tonsillectomy had vitamin D insufficiency.

Reid D, Morton R, Salkeld L, Bartley J.Vitamin D and tonsil disease--preliminary observations. Int J Pediatr Otorhinolaryngol. 2011 Feb;75(2):261-4.

Also, 25(OH)D levels of children with ear infections were about one-half that of community controls.

Cayir A, Turan MI, Ozkan O, Cayir Y, Kaya A, Davutoglu S, Ozkan B.Serum vitamin D levels in children with recurrent otitis media. Eur Arch Otorhinolaryngol. 2013 Mar 30.

In addition, in a prospective study, lower serum 25(OH)D levels were associated with increased risk of laboratory-confirmed respiratory tract infections RTI in children.

Science M, Maguire JL, Russell ML, Smieja M, Walter SD, Loeb M. Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents. Clin Infect Dis. 2013 Aug;57(3):392-7.

As Molloy et al did not use community controls, they did not find lower 25(OH)D levels in children with ASD compared to controls but 3 studies of ASD and 25(OH)D using community controls have found significant differences.

Gong ZL, Luo CM, Wang L, Shen L, Wei F, Tong RJ, Liu Y.Serum 25-hydroxyvitamin D levels in Chinese children with autism spectrum disorders. Neuroreport. 2013 Oct 1.

Meguid NA, Hashish AF, Anwar M, Sidhom G.Reduced serum levels of 25-hydroxy and 1,25-dihydroxy vitamin D in Egyptian children with autism. J Altern Complement Med. 2010 Jun;16(6):641-5.

Mostafa GA, Al-Ayadhi LY.Reduced serum concentrations of 25-hydroxy vitamin D in children with autism: relation to autoimmunity. J Neuroinflammation. 2012 Aug 17;9:201.

On 2016 Aug 30, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed. The ID given is NCT00350855 - the correct ID is NCT00350389. This has been corrected in a subsequent correction published in the originating journal, but not in the PubMed metadata.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database and this ID has been corrected within the journal itself; we hope that this trial’s text and metadata can also be corrected in PubMed.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2018 Jan 03, Denise N Slenter commented:

The information captured in Figure 1 and 2 of this article, is available as a machine readable pathway at the WikiPathways database (https://www.wikipathways.org/index.php/Pathway:WP3933). Figure 3 is available at WikiPathways as well (https://www.wikipathways.org/index.php/Pathway:WP4195). These pathways can be used for data analysis in e.g. Pathvisio (https://doi.org/10.1371/journal.pcbi.1004085) and Cytoscape (https://doi.org/10.1101/gr.1239303).

On 2015 Nov 30, S A Ostroumov commented:

In the paper, it was discovered that the aquatic higher plant (macrophyte) hornwort (other English names: rigid hornwort, coontail, coon's tail; the Latin name: Ceratophyllum demersum) immobilized gold (Au) nanoparticles after their addition to water. This is the first time it was shown that the nanoparticles of gold (Au) in substantial amount bind to the living biomass of the aquatic macrophyte (namely, Ceratophyllum demersum). The concentrations of Au were measured in the samples of the phytomass using neutron activation analysis (NAA). As a result of the binding and/or immobilization of the nanoparticles, the amount of Au in the samples of the phytomass increased manifold (by a factor of 430) above the background level of gold in the plant tissues. The increase was by two orders of magnitude. The new data added some new information to the modern vision of the multifunctional role of the biota in the migration of elements in aquatic ecosystems, and water self-purification. Also, the result added new information to the studies of interactions of Au with organisms that may contribute to new biotechnologies (namely, phytotechnologies to remove heavy metals from water). DOI: 10.1134/S0012496610020158. https://www.researchgate.net/publication/44634488_The_aquatic_macrophyte_Ceratophyllum_demersum_immobilizes_Au_nanoparticles_after_their_addition_to_water;

Some additional key words: nanomaterials, sorption, biosorption, immobilization, environmental chemistry, biogeochemistry, water quality,

On 2016 Jan 12, S A Ostroumov commented:

DOI: 10.1134/S0012496610020158 ;

On 2014 Jan 31, George W Hinkal commented:

The National Cancer Institute has been investing in the development of an online webportal of curated cancer nanotechnology data called caNanoLab. The numerical data and additional nanomaterial characterizations related to this publication have been added to the database and can be found at:

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=41418753&page=0&tab=ALL

https://cananolab.nci.nih.gov/caNanoLab/characterization.do?dispatch=summaryView&sampleId=41418752&page=0&tab=ALL

The left navigation links on these pages provide information about each sample (under Navigation Tree).

For general information on how to use caNanoLab, please visit https://cananolab.nci.nih.gov/caNanoLab/home.jsp

On 2014 Sep 06, David Keller commented:

Are melanoma patients with pre-existing autoimmune disease at increased risk of severe immune reaction to ipilimumab?

Patients with pre-existing autoimmune disease were excluded from this clinical trial. Even so, Grade 3 or 4 immune-related adverse events occurred in 10 to 15% of patients treated with ipilimumab. Is the rate of immune-related adverse events (IRAE) even higher in patients with pre-existing autoimmune disease who are treated with ipilimumab for melanoma? Clinical trials of immune checkpoint inhibitors all exclude such patients, but post-approval data on adverse events could supply an estimate of their relative risk ratio (RRR) with the following equation:

RRR = ( IRAEp / IRAEt ) / (prevalence of AIDM)

where RRR is the relative risk ratio for a severe adverse event in a melanoma patient with preexisting autoimmune disease who is treated with ipilimumab, and IRAEp is the number of immune related adverse events in patients with prior autoimmune disease, IRAEt is the total number of reported immune related adverse events, and the denominator is the prevalence of autoimmune diseases in melanoma patients.

If patients with preexisting autoimmune disease are found to have a significantly elevated relative risk ratio for severe autoimmune reactions to ipilimumab compared with other melanoma patients, they should have access to that information in order to help them make difficult treatment decisions. Each melanoma patient will have their own cut-off of acceptable values for RRR.

Recently, an anti-PD1 immune checkpoint inhibitor, pembrolizumab, was approved by the FDA for advanced melanoma patients who have failed on ipilimumab. It has been suggested that the anti-PD1 agents have a milder autoimmune adverse event profile than anti-CTLA-4 agents like ipilimumab (1,2). If this is true, it may be a reason for patients with active autoimmune diseases to be treated with the former, skipping the latter. If the RRR for a patient with preexisting autoimmune disease is found to be 5, 10 or even 20 times higher than for average patients, then this data could be used to justify treating them with pembrolizumab first-line and off-label.

This question cannot be answered using data from the controlled clinical trials, because patients with active autoimmune diseases were excluded from these studies.

When the FDA approved Yervoy (ipilimumab) in 2011, they mandated a risk mitigation program, including a database of all reported post-approval adverse reactions to Yervoy. In order to obtain full access to the information in that database, one must file a separate request with the FDA, under the Freedom of Information Act (FOIA), for each reported adverse reaction. The number of reports of serious adverse events associated with Yervoy filed from March 2011 through September 2014 totals nearly 4000. Since the cost of filing an FOIA request for each report is over $50, the cost to perform a detailed analysis of the entire database of adverse events is over $20,000. This fee is prohibitive, and defeats the purpose of the risk mitigation program. FDA should provide free access to this data, in order to stimulate and facilitate research into the effects of Yervoy on patient populations which were excluded from the controlled clinical trials.

References

1: Weber J. Review: anti-CTLA-4 antibody ipilimumab: case studies of clinical response and immune-related adverse events. Oncologist. 2007 Jul;12(7):864-72. Review. PubMed PMID: 17673617.

2: Fecher LA, Agarwala SS, Hodi FS, Weber JS. Ipilimumab and its toxicities: a multidisciplinary approach. Oncologist. 2013 Jun;18(6):733-43. doi: 10.1634/theoncologist.2012-0483. Epub 2013 Jun 17. Review. PubMed PMID: 23774827; PubMed Central PMCID: PMC4063401.

On 2017 Sep 20, Jason Stajich commented:

The CRISP software is current available at https://github.com/vibansal/crisp instead of the link in the dead link in the abstract.

On 2015 Apr 15, thomas samaras commented:

None

On 2015 May 22, thomas samaras commented:

Many conflicting studies exist that show shorter people have low coronary heart disease (CHD). Two review papers summarizing findings showing shorter people have less CHD than taller populations are cited below. For example, populations of short people (less than 5'5")that have virtually no CHD include the Solomon Islands, Papua New Guinea, Kalahari Bushmen, Congo Pygmies, and Kitavans. However, with Westernization, some are growing taller and heavier and seeing increases in CHD. Over the last few decades, the Japanese have held the top or third from top ranking for having the lowest CHD in the world.

Women are shorter than men and have lower life-long mortality from CHD. The argument that smaller blood vessels contribute to CHD doesn't seem to apply to women.

The World Cancer Research Fund (2007) has attributed our increased height, weight and chronic disease (including CHD)to our Western diet. They reported that today's chronic diseases are a relatively new occurrence. Trowell also reported that pre-Western people are generally free of Western chronic diseases, including CHD. Burkitt evaluated the medical records from almost 1000 hospitals in the non-developed world and found Western diseases (including CHD) were rare.

The Laron dwarfs in Ecuador have been studied for over 20 years and were found to have no deaths from cancer and diabetes. They also have normal atherosclerosis in spite of being overweight and obese. About 70% of their deaths are from non-age related causes: alcoholism, infections, accidents and neurological disorders.

It is hard to believe that shorter height per se is related to CHD since many studies show that shorter people live longer. These studies include populations in San Diego, Hawaii, Ohio, Spain, Sardinia, and Okinawa. See longevity studies cited below.

Sources

Samaras TT, Elrick H, Storms LH. Is short height really a risk factor for coronary heart disease and stroke mortality? A review. Medical Science Monitor 2004;10:RA63-76.

Samaras TT. Shorter height is related to lower cardiovascular disease risk--a Narrative Review. Indian Heart Journal. 2013; 65: 66-71.

He Q, Morris BJ, Grove JS, et al. Shorter men live longer: Association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. PLOS ONE; 2014:9: 1-8.

Samaras TT. Evidence from eight different types of studies showing that smaller body size is related to greater longevity. Journal of Scientific Research & Reports. 2014;3(16):2150-2160

Salaris L, Poulain, Samaras. Height and survival at older ages among males born in an in-land village in Sardinia. Biodemography and Social Biology. 2012: 58(1): 1-13.

Bartke A. Healthy aging: Is smaller better?--A mini-review. Gerontology.2012; 58:337-43.

On 2017 Aug 04, Luis Mauricio T. R. Lima commented:

This is an interesting article showing human amylin and zinc interaction, and the role of His18 in zinc interaction.

We have recently reported that murine amylin can also interact with zinc, and this peptide has no His18, and interaction is mediated by several other contacts, and can result in modulation of the amyloid aggregation process. https://www.ncbi.nlm.nih.gov/pubmed/27693831 http://dx.doi.org/10.1016/j.bpc.2016.09.008

Collectively, these data suggest an universal amyloid behavior of amylin analogues and interaction with zinc, regardless of the presence of proline or His18.

On 2015 Jul 21, Richard Jenner commented:

Figure S3C of Davidovich C, 2015 shows that the apparent repressive effect of the Xist-RepA stem loop used as a control in Figure 6D of our paper Kanhere A, 2010 is actually due to a mutation of the construct promoter, which we had overlooked. As shown by Davidovich et al, correction of this mutation abolished the apparent repressive activity. Mutations were also found in the short RNA stem loop construct, however, although reduced, the repressive activity of this stem loop remained after these were corrected (Figure S3D of Davidovich C, 2015).

On 2014 Jan 08, Tom Kindlon commented:

There is evidence that CFS patients don't engage in “boom and bust” activity patterns

As Maes and Twisk highlight[1], one part of the Harvey and Wessely model is the contention that CFS patients engage in “boom and bust” activity patterns. This claim has been repeated so often by various individuals that it has been seen as fact by some. But is there actual evidence for it?

What many people may not be aware of is we do have data on the issue. A Dutch study tested a relatively large cohort of CFS patients (n=277) along with 47 healthy controls [2]. The research used actometers to provide an objective measure of activity over 12 days. It found: "Compared to healthy controls, no indication was found that the CFS patients as a group were characterised by a high number of large day-to-day fluctuations in activity."

References:

[1] Maes M, Twisk FN. Chronic fatigue syndrome: Harvey and Wessely's (bio)psychosocial model versus a bio(psychosocial) model based on inflammatory and oxidative and nitrosative stress pathways. BMC Med. 2010 Jun 15;8:35.

[2] van der Werf SP, Prins JB, Vercoulen JH, van der Meer JW, Bleijenberg G. Identifying physical activity patterns in chronic fatigue syndrome using actigraphic assessment. J Psychosom Res. 2000 Nov;49(5):373-9.

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the body of the text of the article. The ID given is NCT00028572. We believe the correct ID, which we have found by hand searching, is NCT00028574.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2017 Mar 05, Boris Barbour commented:

Readers may find the comments/discussion beneath a later paper of interest: Gomes JM, 2016

On 2016 Apr 08, Sergey Mitrofanov commented:

DOI: 10.1142/S0219720010004719 http://www.worldscientific.com/doi/abs/10.1142/S0219720010004719

On 2017 Dec 06, University of Kansas School of Nursing Journal Club commented:

Team Members: Samantha Gibbs, Alyssa Cruz, Annastasia Elliot, Sam Fankhauser, Kelli Fast & Dilnoza Hamraeva [Class of 2018]

The article was selected because it demonstrates how nurse compassion satisfaction, job satisfaction, stress, burnout, and compassion fatigue are related to nurse caring. This relates to our class discussion about factors that are essential to creating a motivational work environment, specifically intrinsic motivators. As future leader, it is important to recognize what motivates others in order to help them grow as a professional nurse. This article explores the relationship between intrinsic motivation and nurse caring which has not been explored in our course.

Intrinsic motivation is an essential aspect to caring for patients. If nurses are to fully advocate for and empower patients, they must be intrinsically motivated and have support from nurse leaders on their unit. This article was selected because the research findings confirm that motivational variables in the work environment are positively correlated with nurse caring and compassion. This increased caring results in overall improved patient care and increased patient satisfaction. The nursing leadership in a work environment is essential to cultivating motivation among staff nurses and must not be overlooked. While extrinsic motivation can be a good starting point, it is the goal that all nurses will eventually operate under conditions of intrinsic motivation, meaning that the nurses are coming to work and caring for patient because they find joy in it. The findings of this study illustrate that fostering a nurse’s intrinsic motivation can result in increased nurse caring behaviors, which will therefore increase patient satisfaction (Burston & Stichler, 2010). Burtson and Stichler state that it is the job of nurse managers to, “reawaken the source of satisfaction that nurses derive from caring, while improving their sense of social belonging” (2010, p. 1829).

As student nurses on the brink of graduation, it is imperative to our professional identity that we understand the systems set in place that motivate workers before accepting a position as an RN. This will allow us as new graduate nurses to feel motivated and empowered in the microsystem and will lead to optimal patient care and increased patient and job satisfaction. Our job satisfaction and intrinsic motivation impacts us personally as well, as we aspire to enjoy work and care for patients in a holistic manner. Even if one is not in a leadership position, future nurses can contribute to the motivational environment by acknowledging coworkers’ achievements and challenging peers to promote growth and life-long learning. If staff nurses and nurse managers promote motivational work environments, the future of nursing practice will naturally begin to foster motivational techniques that will increase both nursing and patient satisfaction as results of improved patient care.

Burston, P. & Stichler, J. (2010). Nursing work environment and nurse caring: Relationship among motivational factors. Journal of Advanced Nursing, 66(8), 1819-1831. doi: 10.1111/j.1365-2648.2010.05336.x

On 2018 Jan 19, Natalie Clairoux commented:

Free version of this article available at http://hdl.handle.net/1866/19738

On 2017 Mar 05, Boris Barbour commented:

Readers may find the comments/discussion beneath a later paper of interest: Gomes JM, 2016

On 2017 Mar 05, Boris Barbour commented:

Readers may find the comments/discussion beneath a later paper of interest: Gomes JM, 2016

On 2014 Dec 17, Sean Ekins commented:

Find out about CDD Vault here https://www.collaborativedrug.com/

On 2014 Dec 17, Sean Ekins commented:

slides on this work slides on this work http://www.slideshare.net/ekinssean/collaborative-drug-discovery-a-platform-for-transforming-neglected-disease-rd-and-beyond

On 2016 May 03, Suresh Panneerselvam commented:

This is very informative article. I enjoyed reading this. Thank you.

On 2014 Feb 28, William Gunn commented:

This study has been chosen for replication by the Cancer Biology Reproducibility Project.

The Cancer Biology Reproducibility Project is a collaboration between the Center for Open Science, Science Exchange, and Mendeley to replicate key experiments from 50 impactful cancer biology studies published between 2010-2012.

To track the progress of this replication, please visit: https://osf.io/yyqas/

To learn more about Cancer Biology Reproducibility Project, including the full list of 50 studies, how the studies were chosen, and details about the people who are managing the project, please visit: https://osf.io/e81xl/wiki/home/

On 2014 Apr 10, Alexander Klabnik commented:

I recommend

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00801358. We believe the correct ID, which we have found by hand searching, is NCT01334658.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2017 Mar 22, Misha Koksharov commented:

There are many interesting further comments: Dworak M, 2011

On 2014 Jan 31, David Simpson commented:

A minor question, but I noticed that a different composition was given for the 4-plex iTRAQ 115 label here in Figure 3 than was given in the classic iTRAQ paper: Ross et al., Mol. Cell. Proteomics 2004, 3, 1154–1169. Has the 4-plex iTRAQ 115 label composition been changed by the manufacturer since the first report was published?

EDIT: To be clear, I'm not doubting the composition given here (it's supported elsewhere: Phanstiel et al., J. Am. Soc. Mass Spectrom. 2008, 19, 1255–1262). I'm just curious about the change from the earliest report.

On 2014 Feb 01, David Simpson commented:

I'm intrigued by the concept discussed here that larger modifications might be inherently more difficult to identify using current search software. Comparing TMT 6-plex with the newer TMT 10-plex, which has the same mass shift, might shed some light on this problem.

On 2014 Sep 22, Thomas Perls, MD, MPH commented:

The corrected version of this work is at: http://www.ncbi.nlm.nih.gov/pubmed/22279548

PLoS One. 2012;7(1):e29848. doi: 10.1371/journal.pone.0029848. Epub 2012 Jan 18. Genetic signatures of exceptional longevity in humans. Sebastiani P1, Solovieff N, Dewan AT, Walsh KM, Puca A, Hartley SW, Melista E, Andersen S, Dworkis DA, Wilk JB, Myers RH, Steinberg MH, Montano M, Baldwin CT, Hoh J, Perls TT.

On 2013 Dec 20, Raphael Stricker commented:

Fatal Clostridium Difficile Colitis Following Treatment for Lyme Disease: The Wrong Message.

Raphael B. Stricker, MD* and Lorraine Johnson, JD, MBA*

*International Lyme and Associated Diseases Society, P.O. Box 341461, Bethesda, MD 20827-1461. www.ILADS.org

Holzbauer and colleagues (1) describe a case of fatal Clostridium difficile colitis in a patient treated with ten weeks of oral antibiotics for chronic Lyme disease. Rather than focusing on patient-specific risk factors and prevention of antibiotic-related complications, the authors preach about the dangers of treating Lyme disease outside the controversial guidelines of the Infectious Diseases Society of America (IDSA), which were the subject of an antitrust investigation by the Connecticut Attorney General (2,3). In doing so, the authors exaggerate the risks of treating Lyme disease and ignore the risks of failing to treat an ongoing spirochetal infection that may cause disability equivalent to congestive heart failure, and even death (4,5). Consequently the emphasis of the case report is misguided and ultimately detrimental to patient care.

In the single case described here, no information is given about cellular or humoral immune dysfunction that may have contributed to the rapid demise of the 52-year-old patient. This rapid demise is unusual in patients less than 80 years old with C. difficile colitis (6) and suggests the presence of a hypervirulent C. difficile ribotype that might explain the clinical course. Furthermore, the authors fail to mention whether the patient received probiotic therapy during the extended oral antibiotic treatment. Probiotic therapy appears to be effective in avoiding antibiotic-induced complications, and evidence suggests that certain probiotics may neutralize C. difficile toxin (7,8). The lack of probiotic therapy may have been a significant factor in this patient’s demise.

As for the appropriateness of antibiotic therapy in a patient with clinical and laboratory evidence of chronic Lyme disease, two points should be considered. First, two approaches to treatment of this tickborne illness have been described in the medical literature. The approach promulgated by IDSA proscribes extended antibiotic therapy for persistent symptoms related to infection with Borrelia burgdorferi, the spirochetal agent of Lyme disease (2). In contrast, the competing approach of the International Lyme and Associated Diseases Society (ILADS) considers this therapy to be appropriate based on evidence of persistent spirochetal infection (4,9,10). Second, the patient described in the report received a course of oral antibiotics that is shorter than the antibiotic courses endorsed or accepted by IDSA for chronic conditions such as tuberculosis, leprosy, complicated actinomycosis, Whipple’s disease, Q fever endocarditis, alveolar echinococcosis, osteomyelitis and asplenia prophylaxis; the risks of prolonged antibiotic therapy are considered acceptable for these conditions (11-18). While several clinical studies have demonstrated the safety of extended oral and intravenous antibiotic therapy for patients diagnosed with Lyme disease (19-22), caution should always be exercised in administering extended antibiotic therapy to any patient with a chronic infectious disease.

References

1. Holzbauer SM, Kemperman MM, Lynfield R. Death due to community-associated Clostridium difficile in a woman receiving prolonged antibiotic therapy for suspected Lyme disease. Clin Infect Dis 2010;51:369-70.

2. Johnson L, Stricker RB. The Infectious Diseases Society of America Lyme guidelines: a cautionary tale about development of clinical practice guidelines. Philos Ethics Humanit Med 2010;5:9.

3. Johnson L, Stricker RB. Final report of the Lyme Disease Review Panel of the Infectious Diseases Society of America: A Pyrrhic victory? Clin Infect Dis 2010;51:1108-9.

4. Cameron DJ. Proof that chronic Lyme disease exists. Interdiscip Perspect Infect Dis 2010;2010:876450.

5. Centers for Disease Control and Prevention (CDC). Three sudden cardiac deaths associated with Lyme carditis - United States, November 2012-July 2013. MMWR Morb Mortal Wkly Rep. 2013;62:993-6.

6. Kotila SM, Virolainen A, Snellman M, Ibrahem S, Jalava J, Lyytikäinen O. Incidence, case fatality and genotypes causing Clostridium difficile infections, Finland, 2008. Clin Microbiol Infect 2011;17:888-93.

7. McFarland LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006;101:812-22.

8. Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human colonic mucosa. Infect Immun 1999;67:302-7.

9. Stricker RB. Counterpoint: Long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clin Infect Dis 2007;45:149-57.

10. Stricker RB, Johnson L. Lyme disease: The next decade. Infect Drug Resist 2011;4:1–9.

11. Small PM, Fujiwara PI. Management of tuberculosis in the United States. N Engl J Med 2001;345:189-200.

12. Cox H, Kebede Y, Allamuratova S, Ismailov G, Davletmuratova Z, Byrnes G, Stone C, Niemann S, Rüsch-Gerdes S, Blok L, Doshetov D. Tuberculosis recurrence and mortality after successful treatment: impact of drug resistance. PLoS Med 2006;3:e384.

13. Garner JP, Macdonald M, Kumar PK. Abdominal actinomycosis. Int J Surg 2007;5:441-8.

14. Freeman HJ. Tropheryma whipplei infection. World J Gastroenterol 2009;15:2078-80.

15. Liu YH, Wang XG, Gao JS, Qingyao Y, Horton J. Continuous albendazole therapy in alveolar echinococcosis: long-term follow-up observation of 20 cases. Trans R Soc Trop Med Hyg 2009;103:768-78.

16. Lazzarini L, Lipsky BA, Mader JT. Antibiotic treatment of osteomyelitis: what have we learned from 30 years of clinical trials? Int J Infect Dis 2005;9:127-38.

17. Price VE, Blanchette VS, Ford-Jones EL.The prevention and management of infections in children with asplenia or hyposplenia. Infect Dis Clin North Am 2007;21:697-710, viii-ix.

18. Beytout J, Tournilhac O, Laurichesse H. Antibiotic prophylaxis in splenectomized adults. Presse Med 2003;32(28 Suppl):S17-9.

19. Donta ST. Tetracycline therapy for chronic Lyme disease. Clin Infect Dis 1997;25 Suppl 1:S52-6.

20. Donta ST. Macrolide therapy of chronic Lyme disease. Med Sci Monit 2003;9:PI136-42.

21. Stricker RB, Green CL, Savely VR, Chamallas SN, Johnson L. Safety of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Minerva Med 2010; 101:1–7.

22. Stricker RB, Delong AK, Green CL, Savely VR, Chamallas SN, Johnson L. Benefit of intravenous antibiotic therapy in patients referred for treatment of neurologic Lyme disease. Int J Gen Med 2011;4:639-46.

Disclosure: RBS is a member of the International Lyme and Associated Diseases Society (ILADS) and a director of LymeDisease.org. He has no financial or other conflicts to declare.

On 2017 Jan 18, CHRISTOPH LANGE commented:

The VEGAS/VEGAS2 software can provide p-values for the top-percentage statistic that are anti-conservative, as the computation of the null-distribution is incorrect. In our technical report, we discuss the issue and provide code that, if included in VEGAS/VEGAS2, will provide correct p-values.

http://biorxiv.org/content/early/2017/01/17/101014

On 2014 Mar 18, Gwinyai Masukume commented:

In Panel 1: Differential diagnoses in severe pre-eclampsia by organ system, malaria is not mentioned.

In some settings, malaria is an important differential diagnosis of severe pre-eclampsia as it can have a significant overlap of clinical and laboratory features with severe pre-eclampsia, for example, headache, nausea, vomiting, intra-uterine growth restriction, thrombocytopenia and raised serum creatinine (1).

Reference: (1) McGready R, Sot M, Ashley EA, Nosten F, Rijken M, Dundorp A. The diagnosis and treatment of malaria in pregnancy. guideline number 54(B). London: Royal College of Obstetricians and Gynaecologists, 2010.

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT00116932. We believe the correct ID, which we have found by hand searching, is NCT00116922.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2014 Mar 02, Zhongheng Zhang commented:

My first paper that is indexed in ISI web of science.

On 2014 Aug 18, Raha Pazoki commented:

Meta-analysis for rs2824292

For those interested, Meta-analysis of the discovery and replication set for the effect of rs2824292 on risk of ventricular fibrillation in this paper can be easily done using meta package in R. The result of the Meta-analysis shows a pooled odds ratio (O.R.) of 1.68 for rs2824292 in the fixed effect model (95% confidence interval [C.I.] = 1.43, 1.97; P value = 2.2×10^-10 ). The random effect model shows similar values (O.R. = 1.67; 95% C.I. = 1.42, 1.98 ; P value = 1.2×10^-9 ).

On 2016 Jan 08, Tom Kindlon commented:

This study uses the (so-called) empiric CFS criteria (Reeves et al., 2005)

Although they don't make it very clear, this study used the Reeves et al. (2005) criteria(1) for defining Chronic Fatigue Syndrome (CFS) (sometimes described by the CDC as an operationalization of the Fukuda et al. (1994) criteria (2)). This can be seen by examining the Reeves et al. (2007) paper on the Georgia cohort (2).

These (Reeves) criteria greatly increased the prevalence of CFS. The "empirical" definition gives a prevalence rate of 2.54% of the adult population(3) compared to 0.235% (95% confidence interval, 0.142%-0.327%) and 0.422% (95% confidence interval, 0.29%-0.56%) when the Fukuda definition (3) was used in previous population studies in the US(4,5).

The definition lacks specificity. For example, one research study(6) found that 38% of those with a diagnosis of a Major Depressive Disorder were misclassified as having CFS using the empirical/Reeves definition. A letter of mine discussed my concerns in more detail(7).

Due to the problems with the criteria, these criteria have not been used by researchers outside those contracted to analyse CDC data (apart from Leonard Jason's research team who studied it and showed problems with it (6)).

References:

1 Reeves WC, Wagner D, Nisenbaum R, Jones JF, Gurbaxani B, Solomon L, Papanicolaou DA, Unger ER, Vernon SD, Heim C. Chronic fatigue syndrome – a clinically empirical approach to its definition and study. BMC Med. 2005;3:19.

2 Reeves WC, Jones JF, Maloney E, Heim C, Hoaglin DC, Boneva RS, Morrissey M, Devlin R. Prevalence of chronic fatigue syndrome in metropolitan, urban, and rural Georgia. Popul Health Metr. 2007 Jun 8;5:5.

3 Fukuda K, Straus SE, Hickie I, Sharpe MC, Dobbins JG, Komaroff A. The chronic fatigue syndrome; a comprehensive approach to its definition and study. Ann Int Med 1994, 121:953-959.

4 Reyes M, Nisenbaum R, Hoaglin DC, Unger ER, Emmons C, Randall B, Stewart JA, Abbey S, Jones JF, Gantz N, Minden S, Reeves WC: Prevalence and incidence of chronic fatigue syndrome in Wichita, Kansas. Arch Int Med 2003, 163:1530-1536.

5 Jason LA, Richman JA, Rademaker AW, Jordan KM, Plioplys AV, Taylor RR, McCready W, Huang CF, Plioplys S. A community-based study of chronic fatigue syndrome. Arch Intern Med. 1999 Oct 11;159(18):2129-37.

6 Jason, LA, Najar N, Porter N, Reh C. Evaluating the Centers for Disease Control's empirical chronic fatigue syndrome case definition. Journal of Disability Policy Studies 2008, doi:10.1177/1044207308325995.

7 Kindlon T. Criteria used to define chronic fatigue syndrome questioned. Psychosom Med. 2010 Jun;72(5):506-7

On 2015 Jul 18, Jan Tunér commented:

In the paper by Kucuk, a laser of 250 mW was used for 48 seconds. This produces energy of 12 J. This parameter is not reported, only the dose of 12 J/cm2. Since the laser aperture is reported to deliver a spot of approximately 10 mm, the dose and the energy in this case gets almost the same numeric value. So far so good. The problem is the understanding of the therapeutic window for biostimulation. The authors cite other researchers and here the complications start. For instance, Hansson used 904 nm, 0.3 mW, 3 minutes. 0.3 x 180 = 0.054 J for clinical use. Mazetto used 780 nm, 70 mW, 10 s, 89.7 J/cm2 = 0.7 J for clinical use. Venanzio used 780 nm, 30 mW, 10 s, 6.3 J/cm2 at three TMJ points. 0.3 x 3 = 0.9 J. The energies in these studies have had to be recalculated since they are not reported in the papers. The three examples above are for TMD arthritic pain. The myalgic studies discussed in the Kucuk paper have the same problem. Now, looking at the energies used in the three studies above, these have been in the range 0.5 - 0.9 J per point. For an average human (keeping in mind that TMD appears to be more common in females) of 60 kg, this would mean approximately 0.2 J per kg. The mean weight of the rabbits was about 3 kg. The 12 joules applied brings 4 joules per kg. For humans this corresponds to 4 x 60 = 180 J! The Arndt-Schultz law stipulates that “For every substance, small doses stimulate, moderate doses inhibit, large doses kill.” The exact optimum for biostimulation of inflammation in the TMJ is not known, but the World Association for Laser Therapy recommends 1-2 points and a total energy of 4 J for clinical use. The TMJ is quite superficial whereas muscles require considerable higher energies due to the poor penetration into these well vasculated tissues. The power density (mW/cm2) is also of importance and low power and longer time are reported to be more effective for tissue repair than high power and short time, even using the same total energy. It is suggested that the lack of effect in the Kucuk paper is due to gross over dosage and subsequent inhibition.

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT0012281. We believe the correct ID, which we have found by hand searching, is NCT00122811.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2014 May 23, Morgan Price commented:

According to the supplementary tables, the mRNA concentration from FISH is poorly correlated with the concentration from RNASeq or with the protein levels. This seems inconsistent with the analyses in Figure 3. In particular, the legend of Figure 3 reports a Pearson correlation of 0.77 between each gene's mRNA FISH level and its protein level. This calculation was done "for genes that express >100 copies of proteins per cell". But when I compute the same correlation coefficient, using the data in Supplementary Table 6, I get a correlation coefficient of just 0.35. (I used the columns "Mean_RNA FISH" and "Mean_Protein", and only the rows with Mean_Protein > 100 and with a Mean_RNA FISH value.)

On 2016 Jun 02, John Tucker commented:

The authors of this paper undertook a survey of published results for trials conducted between January 2000 and December 2006. The results of this survey were that industry-only sponsored studies were more likely to obtain positive results than those partially funded by industry, and that these were in turn more likely to report positive results than those performed without industry funding. The results of this study have been widely cited as evidence that the results of industry funded studies are unreliable and tainted by bias.

A fundamental difficulty with this type of analysis is the underlying assumption that the trials performed by industry and those performed without industry funding are substantially comparable. While the authors do not provide sufficient detail regarding their search criteria to allow perfect recapitulation, a search of the clinicaltrials.gov database with the term "hypercholesterolemia" turns up the following trials.

*93 funded by industry alone, including 39 trials of statins and 32 trials of ezetimibe

*7 funded jointly by industry and some other entity, including trials of orange juice, a high fat diet, and glucosamine as interventions

*7 funded entirely by non-industry entities, including studies of garlic (2x), flaxseed (2x), a high protein diet (2x), and plant sterol-enriched tea as interventions.

Given the vast gulf between the types of interventions being examined and their a priori likelihood of efficacy, the results of studies such as this one should be interpreted with caution.

On 2014 Dec 17, Sean Ekins commented:

Find out about CDD Vault here https://www.collaborativedrug.com/

On 2014 Dec 03, Harri Hemila commented:

A manuscript version is available at HDL

On 2014 Oct 12, GianCarlo Panzica commented:

Effect of the treatment on the vasopressin system of the paraventricular nucleus are described in a following paper: Grassi D, 2014

On 2014 Dec 17, Sean Ekins commented:

This work lead to the development of the open source fingerprints described here http://www.slideshare.net/ekinssean/new-target-prediction-and-vizualization-tools-incorporating-open-source-molecular-fingerprints-for-tb-mobile-version-2

On 2015 Apr 25, James Tsung commented:

Link to corresponding ultrasound videos:<br> https://youtu.be/dPEAh2kuNyY?list=PLHg2xyua_KjtezNYwnO81hVNCS2HrjUi7

On 2017 Mar 05, Boris Barbour commented:

Readers may find the comments/discussion beneath a later paper of interest: Gomes JM, 2016

On 2016 Dec 10, Arnaud Chiolero MD PhD commented:

A comprehensive and bright review of principles of cancer screening. It offers insights on why intuition and common sense mislead health professionnals and patients about the supposed benefits of screening, and why an evidence-based approach is necessary in the assessment of potential benefits and harms of cancer screening.

On 2014 Sep 07, Ivan Oransky commented:

This paper has been retracted, the second of Doo Ok Jang's papers to be retracted: http://retractionwatch.com/2014/09/03/structure-fumble-sinks-second-of-authors-jacs-papers/

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2013 Dec 27, Wichor Bramer commented:

To be a useful addition to a search strategy, sensitive filters should not be too unspecific, and specific filters not too insensitive. Developing a sensitive filter of 100% is no problem, if specificity is not considered, very general filter will find all articles, whether they are positives or negatives, but does not add value to a search, because it does not limit the number needed to read (NNR). And a filter with 100% specificity is easy to create, by taking a very rare phrase that only occurs in one or two positives, but then the sensitivity is almost zero, and the filter is useless.

Simon, Hausner, et al. developed sensitive filters for nurse staffing with a sensitivity of almost 100%, but with a precision of 0.3% the NNR is almost 300, and even for their precise strategy the NNR was 3, with a sensitivity of less than 50%. The authors conclude themselves that 'nurse staffing studies are difficult to identify', but that is true for almost every thematic issue. The low values their filters renders them useless in practice.

The fact that the most precise filter contains the MeSH term Outcome and Process Assessment (Health Care) is related to the fact that this is part of the search strategy of one of the systematic reviews (Kane RL, 2007) that was used to gather the positives, a review of which the presented search strategy is very difficult to read and not repeatable. http://www.ncbi.nlm.nih.gov/books/NBK38310/

On 2014 Dec 10, Kath Wright commented:

Other search filters are available from the InterTASC Information Specialists' Sub-Group Search Filter Resource at https://sites.google.com/a/york.ac.uk/issg-search-filters-resource/home

On 2015 Oct 16, Anne Niknejad commented:

There is an error on Table 1: inversion of gene names between plcA and plcC, plcA gene name should be Rv2351 (not Rv2349 as claimed), and plcC gene name should be Rv2349 (not Rv2351 as claimed)

On 2015 May 04, David Mage commented:

This 1945 paper identified the prone sleeping position as a major risk factor for these infant deaths that were "entirely unexpected," that were first called SIDS by JB Beckwith in 1969. It took some 46 years for the medical profession to rediscover the prone position as a definitive risk factor for SIDS, when SM Beal and CF Finch published "An overview of retrospective case-control studies investigating the relationship between the prone sleeping position and SIDS." J Paediatric Child Health 1991;27:334-339. PMID:1836736

Davison wrote about 318 infants dying in Birmingham, U.K., 1938-1944, as follows: "Quite a number of the children in all groups were found prone or with the face turned into the pillow -- borne out by post-mortem hypostasis -- suggesting death by obstruction to the air passages; and in the absence of other factors one might naturally conclude that death was caused by mechanical means." But that would be wrong because many of these deaths were "found to be respiratory or due to otitis media."

On 2016 Aug 23, Ben Goldacre commented:

This trial has the wrong trial registry ID associated with it on PubMed: both in the XML on PubMed, and in the originating journal article. The ID given is NCT007919689. We believe the correct ID, which we have found by hand searching, is NCT00791986.

This comment is being posted as part of the OpenTrials.net project^[1] , an open database threading together all publicly accessible documents and data on each trial, globally. In the course of creating the database, and matching documents and data sources about trials from different locations, we have identified various anomalies in datasets such as PubMed, and in published papers. Alongside documenting the prevalence of problems, we are also attempting to correct these errors and anomalies wherever possible, by feeding back to the originators. We have corrected this data in the OpenTrials.net database; we hope that this trial’s text and metadata can also be corrected at source, in PubMed and in the accompanying paper.

Many thanks,

Jessica Fleminger, Ben Goldacre*

[1] Goldacre, B., Gray, J., 2016. OpenTrials: towards a collaborative open database of all available information on all clinical trials. Trials 17. doi:10.1186/s13063-016-1290-8 PMID: 27056367

* Dr Ben Goldacre BA MA MSc MBBS MRCPsych<br> Senior Clinical Research Fellow<br> ben.goldacre@phc.ox.ac.uk<br> www.ebmDataLab.net<br> Centre for Evidence Based Medicine<br> Department of Primary Care Health Sciences<br> University of Oxford<br> Radcliffe Observatory Quarter<br> Woodstock Road<br> Oxford OX2 6GG

On 2016 Mar 20, Daniel Schwartz commented:

The HEART SCORE can be calculated online or via a mobile application: http://qxmd.com/calculate/heart-score-chest-pain-in-the-er

Conflict of interest: Medical Director, QxMD

On 2014 Apr 10, Alexander Klabnik commented:

I recommend

On 2013 Oct 24, Robert Tibshirani commented:

This paper presents the coordinate descent approach for fitting the lasso, elastic net, and other related models. It provides the basis for the widely-used glmnet R package

http://cran.r-project.org/web/packages/glmnet/index.html

On 2014 Jan 29, Amanda Capes-Davis commented:

It is really good to see publication of new, authenticated ATC cell lines. The STR data show clearly that these cell lines come from the expected donors. It should be noted though that the STR loci here are not widely used by laboratories worldwide. The ASN-0002 Standard, published by ANSI in 2012, now recommends a consistent set of eight STR loci for cell line authentication testing.

On 2014 Jan 11, Brett Snodgrass commented:

Dear Authors,

Thank you for publication of the excellent article that provides important knowledge about the incidence of VCCs in HLH and their effect on survival.

Please consider that if the VCC results from pathologic alteration of an arterioluminal vessel, then the VCC may not be synonymous with sinusoid as there is no sinusoid involved.

However, if the VCC results from pathologic alteration of an arteriosinusoidal vessel, then the term sinusoid would appropriately apply to only a segment of the VCC. The segment of the VCC closer to the epicardium is presumably derived from the "arterio" segment of the arterio*sinusoidal connection.

VCCs are often used synonymously with VCACs.

1. Ventriculocoronary connections (VCCs)

2. Ventriculocoronary arterial connections (VCACs)

Please provide your kind consideration to the following article published by Joseph Treolar Wearn in 1933. http://bit.ly/JTWearn

Wearn et al. described the myocardial sinusoids and noted that they connected to the arteriosinusoidal vessels but not to the arterioluminal vessels.

The vessels of Wearn include the arterioluminal and arteriosinusoidal vessels. Depending on consensus and further study, they may include a variable segment of the myocardial sinusoids.

Is it possible that some of the VCCs that you describe are not sinusoids but pathologically altered arterioluminal vessels?

My opinion is that we have probably have insufficient information to definitively conclude in every case whether an arteriosinusoidal or arterioluminal vessel is involved.

We have discussed these VCCs (VCACs)in relationship to the hypertensive right ventricle of PAIVS. The vessels of Wearn identified in PAIVS is presumably related to the VCCs that you report in the hypertensive left ventricle of MSAA.

http://www.ncbi.nlm.nih.gov/pubmed/23332812

The vessels of Wearn connect to both the atria and the ventricles. The vessels of Wearn include the VCC (VCACs) and atrio-coronary-connections (atrio-arterio-cameral connections).

If the reader is interested in additional commentary related to these connections, please see the following links:

https://twitter.com/BrettSnodgrass1/status/418829863609331712

https://twitter.com/BrettSnodgrass1/status/421401527035510784

https://twitter.com/BrettSnodgrass1/status/420281076070637568

https://twitter.com/BrettSnodgrass1/status/419599948368183296

My aim is to help produce accurate medical nomenclature and I proposed the term “vessels of Wearn” for the previously unnamed vessels. http://www.ncbi.nlm.nih.gov/pubmed/22704295

In summary, please consider that the term sinusoids may not always be related to the VCCs you describe, but the vessels of Wearn is probably applicable (arteriosinusoidal & arterioluminal connections).

My opinion is that accurate anatomic terminology is a basic principle underlying good medical science, and I ask others to consider whether the aforementioned definitions are appropriate. If this comment is not helpful, please let me know how it might be improved.

Comments and suggestions are welcome.

Thank you kindly.

On 2016 Aug 19, Morten Oksvold commented:

Please note that this article has been retracted and should therefore not be cited in the future.

http://onlinelibrary.wiley.com/doi/10.1002/ijc.30271/full

On 2017 Sep 13, Donald Forsdyke commented:

WHAT IS THEORETICAL BIOLOGY?

In a 2011 letter to the editor, I wrote in a somewhat too boisterous fashion questioning the Editors-in-Chiefs' statement on the nature of theoretical biology. The advent of PubMed Commons now makes it possible to reproduce my unpublished letter, which quotes from their statement:

With 23 papers in the JTB stretching from 1969 to 2009, I am perhaps qualified to congratulate the various Editors who have built on the foundation Professor Danielli so carefully laid in 1961. Yet the letter of the present Editors-in-Chief [1], while claiming to "reflect on the history of theoretical biology," notes that in 1961 "theoretical biology was largely in its infancy."

This will raise many eyebrows – particularly among those of us who have recently celebrated the Darwin Centenary. Apart from Charles Darwin, the many others set rotating in their graves by this remark will include Gregor Mendel, Francis Galton, George Romanes, William Bateson, Herman Muller, JBS Haldane, Theodosius Dobzhansky, McFarlane Burnet and Francis Crick. At a time when "hundreds of our reviewers are women," the disregarding of these past male contributions hints at political correctness.

That the present Editors also consider this "a field based largely on mathematics" would also have struck many of these giants – even Mendel, Galton and Haldane – as bizarre. Thus to the question: "Whether the focus and content of JTB has changed over these fifty years?" one must suspect increasing tendencies to (1) dismiss the history of our subject, (2) follow political agendas, and (3) depart from verbal analysis to mathematical modeling.

It will be interesting to see how many of the experts in the field who have been commissioned by the present Editors to provide reviews of its past, present and future, will note what I believe to have been an unfortunate departure from Danielli’s original goals.

[1] D. Kirschner, Denise Kirschner, Fifty years of JTB: Past, present and future a letter from the editors-in-chief, J. Theor. Biol., (2011) doi:10.1016/j.jtbi.2010.09.004 Kirschner D, 2011

On 2015 May 14, University of Kansas School of Nursing Journal Club commented:

Team 12: Effect of a Quality Improvement Intervention on End of Life Care in the ICU Group 12: Stacy Hanson, Jen Huynh, Sami Johnson, Valerie Melin, Shannan Orpin, Chelsi Puskas, Chandler Schoen

Background: Upon review of this article, our team found many ways that the content within relates to both previous and current discussions in our Nursing in an Evolving Health Care System course. It covers recent class concepts such as quality improvement and previous topics such as creating a healthy work environment and interprofessional collaboration. We chose this article because it relates to many interests and future careers of our fellow peers upon graduation - critical care - and discusses the effect of an intervention that will improve end of life care in the ICU setting. The gap in knowledge that we feel this article attempts to fill is that of how to provide quality end-of-life care and how it affects patient and family mentality when quality of care are both inadequate and exceptional. We are aware that in this specific area of practice, mortality rates are high and studies have shown that quality of the death and dying component of care is far from adequate.

Methods: As a team we searched, CINAHL, PUBMED & ProQuest Nursing & Allied Health Sources. We attempted to initially find an article using keywords such as “Professional Nursing Organizations” and “Professional Nursing Organizations in the healthcare setting” but we were unable to find adequate articles that other members of our class had not already claimed. We attempted a different approach and began typing keywords into the search engine such as “Quality improvement in the nursing setting” and we stumbled upon this five star research article in ProQuest. In this quantitative study, a multifaceted, interdisciplinary, quality-improvement intervention was developed to assess the quality of the death and dying process among twelve random hospitals. This study was an unblended cluster-randomized trial (Curtis et al., 2011). Other aspects that were assessed were that of family satisfaction levels, the patients length of stay in the Intensive Care Unit, how long the patient was on mechanical ventilation and the delay before removing them from this equipment and nine chart-based palliative care elements (Curtis et al., 2011). The intervention specifically focused on clinicians and assessed how five core components were integrated within their care on a day-to-day basis: “clinician education about palliative care In the ICU using a variety of education approaches, identification and raining of ICU clinician local champions for palliative care, academic detailing of nurse and physician ICU directors to address individual ICU-specific barriers to improving end-of-life-care, feedback of individual ICU-specific quality data including family satisfaction, and implementation of system supports such as palliative care order forms” (Curtis et al., 2011, p. 349). The intervention impacts all of the healthcare staff in the ICU setting, family members/loved ones and ultimately the patient during this tough time. As stated earlier, 12 hospitals were chosen randomly. Of those hospitals, six were unsystematically chosen for the intervention to be implemented, while the other six served as the control group. Patients were eligible if they had passed away in the ICU or within thirty hours upon discharge/transfer. If the patient was in the ICU for less than six hours, they were not eligible for the study (Curtis et al., 2011). Data was collected through questionnaires distributed to both nurses and family members of the deceased patient. The questionnaire, The Quality of Dying and Death (QODD), addressed to the family was sent four to six weeks after, measuring their viewpoints on their loved one’s quality of care received during the death and dying process. It also measured their levels of satisfaction with the care they received during their overall time in the ICU setting. The nurses too received the QODD questionnaire, 72 hours after death evaluating their outlook on the care they provided (Curtis et al., 2011).

As a team we found this study to hold high importance so that we as healthcare providers can provide care that is of the utmost respect, granting the last wishes of our patients before they pass away. As nurses, it is an honor to care for someone during the death and dying process, and being a support system that the family and patient can lean on in times of need.

Findings: After the study was implemented and the results were measured, there was no change in the quality of care provided to patients in the ICU setting during the death and dying process. With further research, we identified barriers that may have contributed to this finding. One limitation present throughout this study was the expense and time consumption of randomizing hospitals. Due to this, there was not an adequate sample size to draw appropriate conclusions from, nor equal distribution of patient characteristics. Another constraint found within the study was the complexity of the intervention implemented, making it difficult to measure the success of delivery. This study was also limited to only the United States, making transferability difficult to other regions (Curtis et al., 2011). A few of our team members have experienced the death and dying process internationally upon a service learning experience in Gulu, Uganda, summer of 2014. After reading this article, our team held a unique discussion about quality and quantity of life and the differences in protocols when it comes to dealing with the death and dying process internationally and in the states. Valerie and Stacy discussed their findings, where life-sustaining resources are not available. As a team we talked about how, even though they do not have great technology and resources their quality of life is better because their existence is not prolonged at detrimental costs.

Implications: This literature that our team selected is important to the nursing practice because it provides us with a new perspective on how the death and dying practice can be improved to make the end of life process more accepting. Through this article, we realize how crucial it is to be able to grant the last wishes of a patient. We realize that as future nurses, death is unavoidable and for many of our career trajectories, we will be faced with this situation often. We use this study to acknowledge how important it is to advocate for family members and patients in the most vulnerable times of their life. This research article brings to light the importance of communication among all professions, the importance of patient centered care, and the importance of how quality improvement projects advance the nursing profession. As stated previously, this concept is important on a personal level, so that we can be more aware and sensitive to how we can help family members cope with one of the most difficult situations one ever has to face.

As we transition into the new graduate position, it will be crucial that we can identify areas in need of improvement, that we continuously challenge our practice, searching for the best available evidence and protocols out there to provide patient centered, holistic care. We all are committed to our involvement in quality improvement projects as we strive to be the best nurses we can be.

Reference: Curtis, J. R., Nielsen, E. L., Treece, P. D., Downey, L., Dotolo, D., Shannon, S., Back, A., Rubenfeld G., Engelberg, R. A. (2011). Effect of a quality-improvement intervention on end-of-life care in the intensive care unit: A randomized trial. American Journal of Respiratory and Critical Care Medicine, 183(3), 348-55.

On 2014 Dec 17, Sean Ekins commented:

slides on this work http://www.slideshare.net/ekinssean/collaborative-drug-discovery-a-platform-for-transforming-neglected-disease-rd-and-beyond

On 2014 Feb 12, Preben Berthelsen commented:

This study was registered with ClinicalTrials.gov (NCT00299650). The primary outcome measure was the “Reduction of the mortality rate of ARDS patients at d90”. The result of the investigation was that there was no statistically significant difference between the mortality of patients treated with NMBA or placebo. In the paper, however, the primary outcome measure has been changed to “the adjusted 90-day survival” and this change of the primary outcome measure - from crude to adjusted mortality - results in the statistically significant different mortality rates reported in the paper. In my opinion, we need more compelling and irrefutable valid evidence before we accept that 48 hours of NMBA treatment influences the mortality rate of a complex pathophysiological entity like ARDS. P.G.Berthelsen, MD. Denmark

On 2013 Nov 24, John Sotos commented:

The diagnostic evaluation of the post-partum woman with coronary artery dissection in case 28-2010 (1) was inadequately reported.

I suspect the patient’s cardiac catheterization included aortography, or at least a quick aortic “root shot,” that was not disclosed. Coronary dissection mandates such an evaluation, given its association with simultaneous aortic dissection and with the aortic ectasia seen in heritable disorders of connective tissue (as noted in the case’s table 2). Finding aortic disease would likely have altered this patient’s surgical management.

More concerning, the patient’s physical examination omitted pertinent negatives related to connective tissue disorders that cause aorto-coronary dissections, e.g. body habitus, joint hypermobility, skin laxity, visual acuity, and, remarkably, the bifid uvula of Loeys- Dietz syndrome (2).

Aortic diseases have high mortality when untreated (3). They should always be considered when adults, of any age, have chest discomfort, and should remain in the differential diagnosis even after a coronary dissection is found.

(1) Case records of the Massachusetts General Hospital. Case 28-2010. A 32-year-old woman, 3 weeks post partum, with substernal chest pain. Sabatine MS, Jaffer FA, Staats PN, Stone JR. N Engl J Med. 2010 Sep 16;363(12):1164-73. Pubmed 20843252 doi: 10.1056/NEJMcpc1000966

(2) Aneurysm syndromes caused by mutations in the TGF-beta receptor. Loeys BL, Schwarze U, Holm T, Callewaert BL, Thomas GH, Pannu H, De Backer JF, Oswald GL, Symoens S, Manouvrier S, Roberts AE, Faravelli F, Greco MA, Pyeritz RE, Milewicz DM, Coucke PJ, Cameron DE, Braverman AC, Byers PH, De Paepe AM, Dietz HC. N Engl J Med. 2006 Aug 24;355(8):788-98. Pubmed 16928994

(3) Hirst AD, Johns VJ, Kime SW. Dissecting aneurysm of the aorta: a review of 505 cases. Medicine 1958;37:217-279. Pubmed 13577293