Ter Riet Research Articles

Using preprints in evidence synthesis: Commentary on experience during the COVID-19 pandemic

Using preprints in evidence synthesis: Commentary on experience during the COVID-19 pandemic

Asthma as an outcome: Exploring multiple definitions of asthma across birth cohorts in the Environmental influences on Child Health Outcomes Children's Respiratory and Environmental Workgroup

Asthma definitions vary widely across research studies and feature a trade-off between inclusivity and precision. Harmonizing definitions across multiple asthma birth cohort studies highlights these challenges.

Erratum: Apathy and depressive symptoms in older people and incident myocardial infarction, stroke, and mortality: a systematic review and meta-analysis of individual participant data [Erratum

[This corrects the article DOI: 10.2147/CLEP.S150915.].

Implementing Systematic Review at the National Toxicology Program: Status and Next Steps

The National Toxicology Program (NTP), an interagency program headquartered at the National Institute of Environmental Health Sciences (NIEHS), carries out a broad range of toxicology research and testing and serves as a resource for identification of substances in our environment that are hazards for human health. One of the ways that the NTP identifies hazards is through carrying out literature-based health assessments. Approximately 2 years ago we began exploring systematic-review methodology as a means to enhance transparency and increase efficiency in summarizing and synthesizing findings from studies in our literature-based health assessments. A systematic review uses an explicit, prespecified approach to identify, select, assess, and appraise the data from studies that focus on addressing a specific scientific question (Institute of Medicine 2011). Although traditionally used to grade the quality of evidence and strength of scientific support for recommendations for clinical practice guidelines and healthcare interventions [Agency for Healthcare Research and Quality (AHRQ) 2012; Guyatt et al. 2011; Higgins and Green 2011], we—and others—were interested in how systematic review methodology might be applied to environmental health questions (Agency for Toxic Substances and Disease Registry 2012; National Research Council 2011; Silbergeld and Scherer 2013; U.S. Environmental Protection Agency 2013; Woodruff and Sutton 2011). With the establishment of the Office of Health Assessment and Translation (OHAT) in 2011, the NIEHS launched a new problem-solving resource for the NTP, particularly with respect to identification of noncancer hazards in our environment (Bucher et al. 2011). OHAT took the lead in investigating how systematic review methodology might be used by the NTP. We embraced systematic review methodology as a useful approach for providing thorough documentation of the steps, inputs, and decisions in a literature-based evaluation. However, we also recognized the necessity to extend existing systematic review methods to accommodate our need in environmental health to integrate data from multiple evidence streams (human, animal, in vitro) and focus on observational human studies rather than on the randomized clinical trials more commonly encountered in the field of health-care intervention (NTP 2012a, 2012b). In late February 2013, the NTP released the Draft OHAT Approach for Systematic Review and Evidence Integration for Literature-based Health Assessments – February 2013 [Draft OHAT Approach; Department of Health and Human Services (DHHS) 2013] for public comment; the deadline for receipt of comments is 11 June 2013. The Draft OHAT Approach adopts or adapts guidance from authoritative systematic review groups (AHRQ 2012; Guyatt et al. 2011; Higgins and Green 2011) to handle the breadth of data from human, animal, in vitro, and mechanistic studies relevant for addressing environmental health questions. In developing a draft approach, OHAT sought advice on systematic review through educational webinars and consultation with technical experts, the NTP Executive Committee, a working group of the NTP Board of Scientific Counselors, the NTP Board of Scientific Counselors, and the public. The draft approach involves a seven-step framework for incorporating systematic review methodology into OHAT literature-based health assessments. In early April of 2013, OHAT will release protocols for two case studies to illustrate application of this framework in specific evaluations. We will test our approach in these case studies to help determine whether additional refinement or revision to the Draft OHAT Approach might be needed. To help the public understand the draft approach and protocols, the NTP will hold a web-based informational meeting on 23 April 2013 to provide an overview of the framework, describe the contents of the case-study protocols, and respond to questions (DHHS 2013). Our intent is to carefully consider all public comments received on the draft approach and to present the Draft OHAT Approach to the NTP Board of Scientific Counselors at its meeting on 25–26 June 2013, with discussion by the NTP of any plans to update the document on the basis of the public’s input. Moving forward, our goal is to increase efficiency and provide greater transparency to the rigorous and objective approach that has been the hallmark of OHAT literature-based health assessments.

Lactobacillus probiotics may prevent recurrent UTIs in postmenopausal women

Commentary on: Beerepoot MA, Ter Riet G, Nys S, et al. Lactobacilli vs antibiotics to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in postmenopausal women. Arch Intern Med...

Corrigendum

Corrigendum Siebeling L, Puhan MA, Muggensturm P, Zoller M, ter Riet G. Characteristics of Dutch and Swiss primary care COPD patients – baseline data of the ICE COLD ERIC study. Clin Epidemiol. 2011;3:273–283.Due to two duplicate records, the correct number of patients in the Ice Cold Eric study is 409, not 411. The reported results did not materially change. Those who wish to see the updated tables may contact the corresponding author.Read the original article

Letter to the editor: Pre-operative evaluation of peritoneal deposits using multidetector computed tomography in ovarian cancer. Some considerations

Free AccessCorrespondenceLetter to the editor: Pre-operative evaluation of peritoneal deposits using multidetector computed tomography in ovarian cancer. Some considerationsP Cascales, J Gil and P ParrillaP CascalesSearch for more papers by this author, J GilSearch for more papers by this author and P ParrillaSearch for more papers by this authorPublished Online:28 Jan 2014https://doi.org/10.1259/bjr/26215328SectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail AboutThe Editor,We read with interest the article by Chandrashekhara et al entitled “Pre-operative evaluation of peritoneal deposits using multidetector computed tomography in ovarian cancer“[1]. First we want to congratulate the authors for the in-depth analysis in relation to diagnostic tests (CT) used for the evaluation of patients with peritoneal carcinomatosis from ovarian origin before citoreductive surgery. The article evaluates the role of multidetector CT (MDCT) in identifying peritoneal deposits pre-operatively. However, we would like to make some comments on the results related to the evaluation of diagnostic tests in the published study.We believe that in addition to calculating sensitivity, specificity and predictive values, the coefficients of positive and negative probability (CPP and CPN, respectively) should have been calculated as well. This is because the sensitivity and specificity values, despite completely defining validity (the degree to which a test measures what it is supposed to measure) for the diagnostic test, have the disadvantage of not providing relevant information when it comes to making a clinical decision when faced with a certain test result. The CPP and CPN express a unified summary of sensitivity and specificity, and therefore do not depend on the disease prevalence in each location and permit comparison between different studies, unlike predictive values, which are only valid for the location at which they were calculated [2,3]. In addition, the authors believe that the point estimate of parameters (not including 95%) is valid. This is not entirely correct, since all specific determinations are subject to random error, whose magnitude depends on the sample size and dispersion of individual observations.When we refer to diagnostic test studies, parameters ≥80% are considered to be optimum or high. As we can see, these are optimal only for sensitivity for peritoneal implants or peritoneal thickening in the evaluation of two areas (umbilical and hypogastric region, the latter being at the limit of what may be considered optimum). The reported specificity is acceptable. We can not use the diagnostic test to confirm the presence of peritoneal disease with peritoneal thickening (positive predictive value), although there is a tendency to exclude the presence of disease (negative predictive value) with the information provided, within the margin of error. Based on data from the study, we could not recalculate the data with confidence intervals of 95%, which would be useful to contrast the presence of the null value (that percentage would be 50%) in some of them. This would be interesting for a correct analysis of the data. Nor can we calculate in this way the CPP and CPN, which in turn allow us to compare similar studies.To conclude, we must be careful and methodical with all details involved in a research study in order to contribute efficiently to its comprehensibility and usefulness to the researchers and clinicians for whom it is intended.Yours etc.,References1 Chandrashekhara SH , Thulkar S , Srivastava DN , Kumar L , Hariprasad R , Kumar S , Sharma MC . Pre-operative evaluation of peritoneal deposits using multidetector computed tomography in ovarian cancer. Br J Radiol 2011;84:38–43. Link ISI, Google Scholar2 Moreira J , Bisoffi Z , Narváez A , Van denEnde J . Bayesian clinical reasoning: does intuitive estimation of likelihood ratios on an ordinal scale outperform estimation of sensitivities and specificities? J Eval Clin Pract 2008;14:934–40. Crossref Medline ISI, Google Scholar3 Puhan MA , Steurer J , Bachmann LM , ter Riet G . A randomized trial of ways to describe test accuracy: the effect on physicians' post-test probability estimates. Ann Intern Med 2005;143:184–9. Crossref Medline ISI, Google Scholar Previous article Next article FiguresReferencesRelatedDetailsCited byUse of 18 F-FDG PET/CT in the preoperative evaluation of patients diagnosed with peritoneal carcinomatosis of ovarian origin, candidates to cytoreduction and hipec. A pending issueEuropean Journal of Radiology, Vol. 85, No. 10 Volume 84, Issue 1004August 2011Pages: 677-e168 2011 The British Institute of Radiology History ReceivedJanuary 27,2011AcceptedMarch 07,2011Published onlineJanuary 28,2014 Metrics Download PDF

PubMed is Slightly More Sensitive but More Time Intensive to Search than Ovid MEDLINE

PubMed is Slightly More Sensitive but More Time Intensive to Search than Ovid MEDLINE

Anti-Obesity Drugs: are They Worth It?

Future Medicinal ChemistryVol. 3, No. 3 OpinionAnti-obesity drugs: are they worth it?Mark K Huntington & Roger A ShewmakeMark K Huntington† Author for correspondenceSioux Falls Family Medicine Residency Program, Center for Family Medicine, 1115 East Twentieth Street, Sioux Falls, SD 57110, USA; Department of Family Medicine, Sanford School of Medicine at The University of South Dakota, SD, USA. Search for more papers by this authorEmail the corresponding author at mark.huntington@usd.edu & Roger A ShewmakeSioux Falls Family Medicine Residency Program, Center for Family Medicine, 1115 East Twentieth Street, Sioux Falls, SD 57110, USA; Department of Family Medicine, Sanford School of Medicine at The University of South Dakota, SD, USASearch for more papers by this authorPublished Online:29 Mar 2011https://doi.org/10.4155/fmc.11.5AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: adverse effectscost–effectivenessefficacyobesityweight lossBibliography1 Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity and overweight: updated meta- analysis. BMJ335(7631),1194–1199 (2007).Crossref, Medline, CAS, Google Scholar2 O’Meara S, Riemsma R, Shirran L, Mather L, ter Riet G. A rapid and systematic review of the clinical effectiveness and cost-effectiveness of orlistat in the management of obesity. Health Technology Assessment5(18),1–81 (2001).Crossref, Google Scholar3 Escott-Stump S. Nutrition and Diagnosis-Related Care. Lippincott Williams & Wilkins, PA, USA (2002).Google Scholar4 Hill JO, Hauptman J, Anderson JW et al. Orlistat, a lipase inhibitor, for weight maintenance after conventional dieting: a 1-y study. Am. J. Clin. Nutr.69(6),1108–1116 (1999).Crossref, Medline, CAS, Google Scholar5 Mechcatie E. FDA panel gives thumbs down to lorcaserin. Family Practice News40(17),9 (2010).Crossref, Google Scholar6 Turley A. Obesity drugs strive for US approval. Chemistry World7(9),2 (2010).Google Scholar7 Bray GA. Medications for obesity: mechanisms and applications. Clin. Chest Med.30(3),525–538 (2009).Crossref, Medline, Google Scholar8 Huntington MK, Shewmake RA. Weight-loss supplements: what is the evidence? S. D. Med.63(6),205–207 (2010).Medline, Google Scholar9 DeLaet D, Schauer D. Obesity in adults. Am. Fam. Physician.82(8),974–975 (2010).Google Scholar10 Pillitteri JL, Shiffman S, Rohay JM, Harkins AM, Burton SL, Wadden TA. Use of dietary supplements for weight loss in the United States: results of a national survey. Obesity (Silver Spring)16(4),790–796 (2008).Crossref, Medline, CAS, Google Scholar11 Blanck HM, Serdula MK, Gillespie C et al. Use of nonprescription dietary supplements for weight loss is common among Americans. J. Am. Diet. Assoc.107(3),441–447 (2007).Crossref, Medline, Google Scholar12 Pi-Sunyer X, Kris-Etherton P. Improving health outcomes: future directions in the field. J. Am. Diet. Assoc.105(5 Suppl. 1),S14–S16 (2005).Crossref, Medline, Google Scholar13 Greenway FL, Ryan DH, Bray GA, Rood JC, Tucker EW, Smith SR. Pharmaceutical cost savings of treating obesity with weight loss medications. Obes. Res.7(6),523–531 (1999).Crossref, Medline, CAS, Google Scholar14 Avenell A, Broom J, Brown TJ et al. Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement. Health Technology Assessment8(21),1–182 (2004).Crossref, Google Scholar15 Welbourn R, Pournaras D. Bariatric surgery: a cost-effective intervention for morbid obesity; functional and nutritional outcomes. Proc. Nutr. Soc.69(4),528–535 (2010).Crossref, Medline, Google Scholar16 Tsai AG, Asch DA, Wadden TA. Insurance coverage for obesity treatment. J. Am. Diet. Assoc.106(10),1651–1655 (2006).Crossref, Medline, Google Scholar101 Orexigen Therapeutics, Inc. CONTRAVE® Advisory Meeting Briefing Document (2010). Link.Google Scholar102 Tucker J. Arena pharma: understanding the market for anti-obesity drugs. 3rd September (2010). http://seekingalpha.com/article/223715-arena-pharma-understanding-the-market-for-anti-obesity-drugs (Accessed 3 December 2010).Google Scholar103 ScienceDaily. No evidence that popular slimming supplements facilitate weight loss, new research finds. 14th July (2010). www.sciencedaily.com/releases/2010/07/100712103445.htm (Accessed 3 December 2010).Google ScholarFiguresReferencesRelatedDetailsCited ByThe effects of medicinal herbs on gut microbiota and metabolic factors in obesity models: A systematic reviewDiabetes & Metabolic Syndrome: Clinical Research & Reviews, Vol. 16, No. 9Antiobesity Effects of Natural Products from an Epigenetic Perspective4-Aminophthalazin-1(2H)-one Derivatives as Melanin Concentrating Hormone Receptor 1 (MCH-R1) AntagonistsBulletin of the Korean Chemical Society, Vol. 34, No. 12Small molecule drug screening in Drosophila identifies the 5HT2A receptor as a feeding modulation target2 July 2013 | Scientific Reports, Vol. 3, No. 1Synthesis and SAR study of pyrrolo[3,4-b]pyridin-7(6H)-one derivatives as melanin concentrating hormone receptor 1 (MCH-R1) antagonistsBioorganic & Medicinal Chemistry Letters, Vol. 23, No. 6Lipolytic proteomics5 March 2012 | Mass Spectrometry Reviews, Vol. 31, No. 5Limitations in anti-obesity drug development: the critical role of hunger-promoting neurons3 August 2012 | Nature Reviews Drug Discovery, Vol. 11, No. 9Management of Obesity in the National Health and Nutrition Examination Survey (NHANES), 2007–2008Annals of Epidemiology, Vol. 22, No. 5 Vol. 3, No. 3 Follow us on social media for the latest updates Metrics Downloaded 618 times History Published online 29 March 2011 Published in print March 2011 Information© Future Science LtdKeywordsadverse effectscost–effectivenessefficacyobesityweight lossFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download

Clinical Usefulness of the Ottawa Ankle Rules for Detecting Fractures of the Ankle and Midfoot

Abstract Reference: Bachmann LM, Kolb E, Koller MT, Steurer J, ter Riet G. Accuracy of Ottawa Ankle Rules to exclude fractures of the ankle and mid-foot: systematic review. BMJ. 2003;326(7386):417–423. Clinical Question: What is the evidence for the accuracy of the Ottawa Ankle Rules as a decision aid for excluding fractures of the ankle and midfoot? Data Sources: Studies were identified by searching MEDLINE and PreMEDLINE (Ovid version: 1990 to present), EMBASE (Datastar version: 1990–2002), CINAHL (Winspires version: 1990–2002), the Cochrane Library (2002, issue 2), and the Science Citation Index database (Web of Science by Institute for Science Information). Reference lists of all included studies were also searched, and experts and authors in the specialty were contacted. The search had no language restrictions. Study Selection: Minimal inclusion criteria consisted of (1) study assessment of the Ottawa Ankle Rules and (2) sufficient information to construct a 2 × 2 contingency table specifying the false-positive and false-negative rates. Data Extraction: Studies were selected in a 2-stage process. First, all abstracts and titles found by the electronic searches were independently scrutinized by the same 2 authors. Second, copies of all eligible papers were obtained. A checklist was used to ensure that all inclusion criteria were met. Disagreements related to the eligibility of studies were resolved by consensus. Both authors extracted data from each included study independently. Methods of data collection, patient selection, blinding and prevention of verification bias, and description of the instrument and reference standard were assessed. Sensitivities (using the bootstrap method), specificities, negative likelihood ratios (using a random-effects model), and their standard errors were calculated. Special interest was paid to the pooled sensitivities and negative likelihood ratios because of the calibration of the Ottawa Ankle Rules toward a high sensitivity. Exclusion criteria for the pooled analysis were (1) studies that used a nonprospective data collection, (2) unknown radiologist blinding (verification bias), (3) studies assessing the performance of other specialists (nonphysicians) using the rules, and (4) studies that looked at modifications to the rules. Main Results: The search yielded 1085 studies, and the authors obtained complete articles for 116 of the studies. The reference lists from these studies provided an additional 15 studies. Only 32 of the studies met the inclusion criteria and were used for the review; 5 of these met the exclusion criteria. For included studies, the total population was 15 581 (range = 18–1032), and average age ranged from 11 to 31.1 years in those studies that reported age. The 27 studies analyzed (pooled) consisted of 12 studies of ankle assessment, 8 studies of midfoot assessment, 10 studies of both ankle and midfoot assessment, and 6 studies of ankle or midfoot assessment in children (not all studies assessed all regions). Pooled sensitivities, specificities, and negative likelihood ratios for the ankle, midfoot, and combined ankle and midfoot are presented in the Table. Based on a 15% prevalence of actual fracture in patients presenting acutely after ankle or foot trauma, less than a 1.4% probability of fracture existed. Because limited analysis was conducted on the data from the children, we elected to not include this cohort in our review. Conclusions: Evidence supports the use of the Ottawa Ankle Rules as an aid in ruling out fractures of the ankle and midfoot. The rules have a high sensitivity (almost 100%) and modest specificity. Use of the Ottawa Ankle Rules holds promise for saving time and reducing both costs and radiographic exposure without sacrificing diagnostic accuracy in ankle and midfoot fractures.

Nitric Oxide Is Critical for Inducing Phosphatidic Acid Accumulation in Xylanase-elicited Tomato Cells

Nitric Oxide (NO) is a second messenger related to development and (a)biotic stress responses in plants. We have studied the role of NO in signaling during plant defense responses upon xylanase elicitation. Treatment of tomato cell cultures with the fungal elicitor xylanase resulted in a rapid and dose-dependent NO accumulation. We have demonstrated that NO is required for the production of the lipid second messenger phosphatidic acid (PA) via the activation of the phospholipase C (PLC) and diacylglycerol kinase (DGK) pathway. Defense-related responses downstream of PA were studied. PA and, correspondingly, xylanase were shown to induce reactive oxygen species production. Scavenging of NO or inhibition of either the PLC or the DGK enzyme diminished xylanase-induced reactive oxygen species production. Xylanase-induced PLDbeta1 and PR1 mRNA levels decreased when NO or PA production were compromised. Finally, we have shown that NO and PA are involved in the induction of cell death by xylanase. Treatment with NO scavenger cPTIO, PLC inhibitor U73122, or DGK inhibitor R59022 diminished xylanase-induced cell death. On the basis of biochemical and pharmacological experimental results, we have shown that PLC/DGK-derived PA represents a novel downstream component of NO signaling cascade during plant defense.

Presentation of Diagnostic Test Accuracy

Letters7 February 2006Presentation of Diagnostic Test AccuracyMike Broce, BS and Bernardo Reyes, MDMike Broce, BSFrom CAMC Institute, Charleston, WV 25304.Search for more papers by this author and Bernardo Reyes, MDFrom CAMC Institute, Charleston, WV 25304.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-144-3-200602070-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:We agree with Dr. Puhan and his colleagues (1) that it is essential for physicians to interpret the real value of diagnostic testing to confirm clinical suspicions so that a better practice of medicine can occur. After reading their conclusions, we believe that replication of their results is needed, perhaps with a few modifications. Our suggestions are not intended to diminish the findings of what we consider to be an excellent study.Although a table for the clinical vignettes was provided, it was not clear if equations to calculate illness probability changes were provided to surveyed physicians. ...Reference1. Puhan MA, Steurer J, Bachmann LM, ter Riet G. A randomized trial of ways to describe test accuracy: the effect on physicians' post-test probability estimates. Ann Intern Med. 2005;143:184-9. [PMID: 16061916] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Mike Broce, BS; Bernardo Reyes, MDAffiliations: From CAMC Institute, Charleston, WV 25304.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA Randomized Trial of Ways To Describe Test Accuracy: The Effect on Physicians' Post-Test Probability Estimates Milo A. Puhan , Johann Steurer , Lucas M. Bachmann , and Gerben ter Riet Presentation of Diagnostic Test Accuracy Daniel J. Brotman Presentation of Diagnostic Test Accuracy Milo A. Puhan , Johann Steurer , and Gerben ter Riet Metrics 7 February 2006Volume 144, Issue 3Page: 220-221KeywordsConflicts of interestDiagnostic medicineForecastingMedical conditionsReproducibility ePublished: 7 February 2006 Issue Published: 7 February 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...

The Transcriptional Response of Saccharomyces cerevisiae to Pichia membranifaciens Killer Toxin

The transcriptional response of Saccharomyces cerevisiae to Pichia membranifaciens killer toxin (PMKT) was investigated. We explored the global gene expression responses of the yeast S. cerevisiae to PMKT using DNA microarrays, real time quantitative PCR, and Northern blot. We identified 146 genes whose expression was significantly altered in response to PMKT in a non-random functional distribution. The majority of induced genes, most of them related to the high osmolarity glycerol (HOG) pathway, were core environmental stress response genes, showing that the coordinated transcriptional response to PMKT is related to changes in ionic homeostasis. Hog1p was observed to be phosphorylated in response to PMKT implicating the HOG signaling pathway. Individually deleted mutants of both up- (99) and down-regulated genes (47) were studied for altered sensitivity; it was observed that the deletion of up-regulated genes generated hypersensitivity (82%) to PMKT. Deletion of down-regulated genes generated wild-type (36%), resistant (47%), and hypersensitive (17%) phenotypes. This is the first study that shows the existence of a transcriptional response to the poisoning effects of a killer toxin.

Coughing In Pre-School Children in General Practice: When Are RAST’s for Inhalation Allergy Indicated?

Eysink PE, Bottema BJ, ter Riet G, Aalberse RC, Stapel SO, Bindels PJ. Pediatr Allergy Immunol . 2004;15:394–400 To identify patterns of clinical history associated with extreme (high or low) probabilities of allergic sensitization in coughing children to restrict allergy testing to those with an intermediate probability of sensitization. A total of 752 children in the Netherlands, aged 1 to 4 years, visiting their general …

Phospholipase D Is a Negative Regulator of Proline Biosynthesis in Arabidopsis thaliana

Accumulation of proline has been observed in a large number of plant species in response to drought and salt stresses, suggesting a key role of this amino acid in plant stress adaptation. Upstream components of the proline biosynthesis signal transduction pathways are still poorly defined. We provide experimental evidence that phospholipase D (PLD) is involved in the regulation of proline metabolism in Arabidopsis thaliana. The application of primary butyl alcohols, which divert part of PLD-derived phosphatidic acid by transphosphatidylation, stimulated proline biosynthesis even without hyperosmotic constraints. Moreover, application of primary butyl alcohols enhanced the proline responsiveness of seedlings to mild hyperosmotic stress. These data indicate that some PLDs are negative regulators of proline biosynthesis and that plants present a higher proline responsiveness to hyperosmotic stress when this regulator is abolished. We clearly demonstrate that PLD signaling for proline biosynthesis is similar to RD29A gene expression and different from the abscisic acid-dependent RAB18 gene expression. Our data reveal that PLDs play positive and negative roles in hyperosmotic stress signal transduction in plants, contributing to a precise regulation of ion homeostasis and plant salt tolerance.

A negative result on the Ottawa knee rules excludes fracture in patients with acute knee injury

Summary of Bachmann LM, Haberzeth S, Steurer J and ter Riet G (2004): The accuracy of the Ottawa knee rule to rule out knee fractures. A systematic review. Annals of Internal Medicine 140: 121–124. [Prepared by Chris Maher, Editorial Board Member]

Restricted Randomization in Randomized Controlled Trials-Reply

<h3>In Reply.</h3> —We thank Drs ter Riet and Kessels for attempting to explain the similar sample sizes we found in treatment and control groups. Unfortunately, their suggestion of widespread use of a form of restricted randomization does not shed any new light on our findings. In our original article, we stated, "The strong tendency for the comparison groups to be of equal or similar sizes may be explained by unreported use of (1) restriction, usually blocking...." That explanation includes the model postulated by ter Riet and Kessels, which is just one of many different forms of restriction. Ter Riet and Kessels observe that our "model does not reflect randomized trial conduct in practice." Indeed, that just restates our main argument. The authors of the 96 reports stated or (more usually) implied use of simple, unrestricted randomization. Thereby, they, not we, specified the form of the model used. Furthermore, our approach

Ultrasound treatment for pressure ulcers

EDITOR,--Gerben ter Riet and colleagues report a double blind randomised trial of ultrasound treatment and placebo in 88 patients with pressure ulcers; they found no significant differences between the treatments.1 They also indicate that a tentative suggestion made by McDiarmid et al after a similar trail in 44 patients some 10 years ago, in relation to the differential efficacy of ultrasound treatment (US) in infected ulcers, was not substantiated.2 Both these findings come as no surprise in view …

What Kind of Control Condition should we use in Trials of Acupuncture?

Disappointingly little has been achieved by literally hundreds of attempts to evaluate acupuncture for chronic pain. Major methodological flaws are apparent in the vast majority of studies. Controlled studies have shown positive findings for low back pain, and equivocal results for migraine and asthma. Nevertheless larger scale studies are warranted for all these disorders, though other types of musculo-skeletal pain, tension headache and arthritis are also possible candidates.Controlled trials of any treatment have become an immensely difficult and technical undertaking. They are expensive, time-consuming and ideally require the collaboration between practitioners and researchers and consultation with a statistician. It is not really possible for acupuncturists in private practice to mount such trials, and it is very difficult for a professional association or college. However, it is clear that there is no longer any point in conducting small, preliminary studies of acupuncture treatment. There are dozens of such studies, with some encouraging findings. The only way acupuncture can gain full acceptance as a valid form of treatment is through good controlled trials that are large enough to answer the questions they pose.Ter Riet's list of criteria as a good starting point for anyone designing a trial of acupuncture. Specific points I would emphasize after reviewing the existing research on acupuncture are:1. Trials should be single blind; it is not feasible to conduct double-blind trials. Some trials are nevertheless incorrectly described as double blind.2. A range of outcome measures should be used, preferably with some independent assessment. An adequate follow-up is essential.3. Considerable care needs to be taken in the choice of control group, especially with placebo controls. For a placebo I suggest a form of acupuncture treatment that is designed to have minimal effects. It will be the option that is the closest match to the true treatment and avoids the difficulties inherent in randomizing patients to a non-acupuncture treatment.4. It is very useful to check the adequacy of any control treatment with a measure of credibility, or similar assessment, as the choice of control is frequently a matter for criticism.5. Trials have generally been too small to permit firm conclusions. Ter Riet (Ter Riet, Kleijnen et al. 1990) implies that 50 patients per group are needed. This may not be necessary. However preliminary calculations of the necessary size for a reasonable power need to be carried out.