Letters to the Editor Metaldehyde exposures
On behalf of Lonza Incorporated, the manufacturer of technical-grade metaldehyde, I want to express concerns with the recent article by Buhl et al1 on the decrease in the number of reports of metaldehyde exposures to dogs and add some additional information concerning metaldehyde. The article states that, as reflected in National Pesticide Information Center (NPIC) data, “an apparent increase in the number of [metaldehyde exposure incident] reports was observed each year between 2001 and 2005, followed by decreasing numbers thereafter.” The authors further state, “New precautionary language for metaldehyde product labels, required by the US EPA beginning in 2006 and 2007, may have contributed to the apparent decrease in the number of exposure incidents reported to NPIC beginning in 2006.” We believe that the latter statement is incorrect and that there is no correlation between the decrease in the number of reported incidents and the new precautionary labeling, which was introduced later than the stated time. In its 2006 metaldehyde reregistration eligibility decision authorizing the continued use of metaldehyde, the EPA mandated that specific precautionary language and a dog warning symbol be added to labels on metaldehyde products intended for home garden use.2,3 After the reregistration eligibility decision was finalized, metaldehyde registrants needed time for the EPA to review and approve label changes as required under federal law for each registered product. After US EPA approval was obtained, registrants also had to obtain state registration agency approval of their amended labels. Finally, once the state agencies approved these amended labels, additional time passed before products with new labels including the new precautionary language entered the retail market. 478
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As a result, the first commercial home garden metaldehydecontaining product (a carbarylmetaldehyde combination) to carry a label with the new precautionary language was not released until 2010.a,b Other metaldehyde-containing products were not updated with the new precautionary language warning against exposure for dogs until September 2012, and for some metaldehyde-containing home garden products, a revised label incorporating this precautionary language still has not been adopted.b Buhl et al1 report that the number of metaldehyde exposure reports stated in NPIC data began to decrease in 2006. Because metaldehyde-containing home garden products carrying the revised precautionary language were not in commercial use until 2010, and even later for some products, it seems likely that the precautionary language cannot have contributed to the existing decrease in the number of exposures reported by the NPIC. Kari Mavian, BS Head of Regulatory Assurance Americas Lonza Inc Allendale, NJ a.
Pesticide Product Label System (PPLS) [database online]. Washington, DC: US EPA, 2013. Available at: iaspub.epa. gov/apex/pesticides/f?p=PPLS:1. Accessed Jun 11, 2013.
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Pesticide, Ingredient, and Manufacturer System (PIMS) [database online]. Ithaca, NY: New York State Department of Environmental Conservation, 2013. Available at: pims.psur.cornell.edu/ index.php. Accessed Jun 11, 2013.
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Buhl KJ, Berman FW, Stone DL. Reports of metaldehyde and iron phosphate exposures in animals and characterization of suspected iron toxicosis in dogs. J Am Vet Med Assoc 2013;242:1244–1248. Metaldehyde reregistration eligibility decision: notice of availability (EPAHQ-OPP-2005-0231-0011). Fed Regist 2006;71:45551. Metaldehyde; amendment and closure of reregistration eligibility decision: notice of availability (ID: EPA-HQOPP-2005-0231-0030). Fed Regist 2007;72:37012.
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The authors respond: My coauthors and I wish to thank Ms. Mavian for her comments. We were interested to learn that some metaldehyde-containing pesticide product labels had not been updated six years after the US EPA finalized its reregistration eligibility decision for metaldehyde.1 According to EPA records,a,b 17 primary end-use product registrations containing metaldehyde are active, and labels for three of them have been updated in accordance with the reregistration eligibility decision, which was amended and finalized in 2007. Other revisions may be under federal review, and label review and registration at the state level would also be required.
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The impetus for our study2 was concerns about reported animal exposures to molluscicides. Although we were not able to evaluate causes for the decrease in the number of reports of animal exposures to metaldehyde, we would offer a few alternative hypotheses in light of Ms. Mavian’s comments. First, according to the reregistration eligibility decision,1 the amount of bittering agent (denatonium benzoate) in technical-grade metaldehyde was increased 10-fold in 2003 from 30 to 300 mg/g. That increase may have been an important factor in the decrease in exposure incidents from 2006 through 2011, particularly if it took two or more years to achieve market penetration with the new formulation. Second, there currently are two primary product registrations for pesticides containing iron phosphate, both of which are distributed under a variety of brand names. One of the products was first registered in 1997; the other was first registered in 2006. It is possible that metaldehyde exposure incidents decreased between 2006 and 2011 because consumers had increased access to products containing an alternate active ingredient. It is always positive to see pesticide exposure reports decrease over time. Pet owners can contribute to that decrease by exercising vigilance, storing pesticide products properly, and following all label instructions. This guidance applies to pesticides that are labeled as organic as much as it applies to conventional pesticides. Veterinarians can contribute through ongoing educational efforts. Kaci J. Buhl, MS Oregon State University Corvallis, Ore a.
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Pesticide Product Information System [database online]. Washington, DC: US EPA, 2013. Available at: www.epa.gov/ opp00001/PPISdata. Accessed Jul 2, 2013. Pesticide Product Label System (PPLS) [database online]. Washington, DC: US EPA, 2013. Available at: iaspub.epa. gov/apex/pesticides/f?p=PPLS:1. Accessed Jul 2, 2013. US EPA Office of Prevention, Pesticides, and Toxic Substances. Reregistration eligibility decision for metaldehyde. Washington, DC: US Government Printing Office, 2006.
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Buhl KJ, Berman FW, Stone DL. Reports of metaldehyde and iron phosphate exposures in animals and characterization of suspected iron toxicosis in dogs. J Am Vet Med Assoc 2013;242:1244–1248.
Surgical versus nonsurgical management for overweight dogs with cranial cruciate ligament rupture
As veterinary surgeons, we read with great interest the study by Wucherer et al1 regarding surgical versus nonsurgical management for overweight dogs with cranial cruciate ligament rupture. We believe that the authors may have overestimated the benefit of surgical treatment (tibial plateau leveling osteotomy), relative to nonsurgical management, through their use of outcome measures that combined subjective and objective assessments. We were struck by the fact that the subjective assessments favored surgery, but analysis of objective measurements (ie, force-plate measurement of ground reaction forces) did not. In their discussion, the authors did not address the potential role of placebo effects by proxy in the reported subjective improvements. For obvious reasons, participants in this study were not blinded to the treatment group assignment. But, given that clinical differences between the two groups were modest, it seems possible that if study participants had been blinded, the apparent benefit of surgery might have disappeared altogether. Simon J. Baker, MA, VetMB, PhD House and Jackson Veterinary Surgeons Blackmore, Essex, England Gordon J. Baker, BVSc, PhD, DACVS Professor Emeritus of Equine Medicine and Surgery University of Illinois Urbana, Ill
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Wucherer KL, Conzemius MG, Evans R, et al. Short-term and long-term outcomes for overweight dogs with cranial cruciate ligament rupture treated surgically or nonsurgically. J Am Vet Med Assoc 2013;242:1364– 1372.
Use of marijuana in complementary and alternative veterinary medicine
I recently took in an older Thoroughbred as a boarder on my farm. When it arrived, the horse had a low body condition score, signs of anxiety attributed to the move, and evidence of a mildly sore foot. As a practitioner of traditional Chinese veterinary medicine, it occurred to me that marijuana could potentially relieve the horse’s stress, promote appetite, and provide analgesia. To my surprise, that same day my June 15 issue of JAVMA arrived with Scott Nolen’s news article1 on veterinary marijuana. Thank you for opening the door to discussion of this herb. Many people today use marijuana for medicinal purposes, and it seems likely that our patients will be exposed to marijuana if their owners use it. Thus, regardless of whether we think marijuana has therapeutic uses in animals, we need to understand the effects it has in animals and the risks associated with its use. At the same time, we should keep an open mind about what may yet become a new therapeutic tool for pets. I believe that veterinarians should be leaders in advocating for the ability to use our knowledge, training, and professional judgment to choose therapeutic tools on behalf of our patients. There is a long history of marijuana use in animals, and much is known about its actions, safety profile, and risks. However, individual cannabinoids likely do not have the same effects as the whole plant. Therefore, encouraging research into isolated compounds that can be synthetically created is probably not as useful as encouraging research on the marijuana plant as a whole. Also, plant strains vary and can potentially be tailored so as to, for instance, provide relief for nausea and stomach pain versus general pain relief and sedation.2 What is needed is decriminalization of marijuana so that its potential as a therapeutic tool can be further investigated. Indeed, if we collaborate with our colleagues in China, as Drs. Memon and Xie recommend in the same issue,3 we may learn much Views: Letter to the Editor
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from their long history of veterinary herbal medicine and be global leaders in affordable, accessible care. I’m proud of my profession and the brave colleagues who are opening this dialogue. Jackie Casanova, DVM Mobile Veterinary Care Gainesville, Fla 1. 2.
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Nolen RS. Veterinary marijuana? J Am Vet Med Assoc 2013;242:1605–1609. American College of Physicians. Supporting research into the therapeutic role of marijuana (position paper). Philadelphia: American College of Physicians, 2008. Memon MA, Xie H. Prospects for collaboration between the veterinary professions in the United States and China. J Am Vet Med Assoc 2013;242:1632– 1634.
Pathological optimism
Legend has it that the notorious Roman emperor Nero played the fiddle during the Great Fire of Rome in 64 AD, and the saying “fiddling while Rome burns” has been used to describe someone engaged in unproductive pursuits during times of need. Of course, the violin wasn’t invented until many years after the time of the Great Fire, and history suggests that Nero may not even have been in the city at the time. Nevertheless, it still seems an apt metaphor for the veterinary profession in the 21st century. Weaknesses, threats, and opportunities for beneficial changes—in veterinary education in particular—have repeatedly been identified in past decades, but like Nero, we paid scant attention. Peter Eyre, DVM&S, BVMS, BSc, PhD Blacksburg, Va
Additional variables identified as significant predictors of successful return of spontaneous circulation in cardiac arrest and resuscitation
Previously, we reported the results of a 5-year prospective study of cardiac arrest and resuscitation at the University of Georgia.1 In that
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study, data were analyzed by means of logistic regression with stepwise analysis to identify variables associated with the successful return of spontaneous circulation (ROSC). With this method, an initial model containing all variables is constructed, and variables are sequentially removed. However, when variables are selected for removal, all of the possible information contained in that variable is also removed, which can decrease the validity and precision of the final model and deprive the results of potentially valuable information. Numerous statistical methods have been used to address this weakness of standard variable selection methods, including the stepwise method, but there is no single solution that is superior for all data sets.2 We recently reported the results of a more detailed analysis of this data set that used logistic group bridge regression for variable selection instead of stepwise logistic regression.3 With this method, variables are not immediately removed from the model, although certain penalties are imposed that can eventually result in removal of a variable, and as a result of the new analysis, more variables were identified as being significant predictors of ROSC. In the original study,1 treatment with mannitol, lidocaine, fluids, dopamine, corticosteroids, and vasopressin; duration of CPR effort; whether cardiopulmonary arrest occurred while the patient was anesthetized; number of doses of epinephrine; the presence of multiple disease conditions; lateral recumbency for chest compressions; and suspected cause of arrest were all found to be significant variables in the logistic regression model. With the new analysis, the following variables that were not previously included were selected to be in the model: dead on arrival (OR, 0.06); initial arrhythmia characterized as asystole (OR, 0.17), electromechanical dissociation (OR, 0.02), ventricular fibrillation (OR, 0), ventricular tachycardia (OR, 72,000), bradycardia (OR, 0.17), or atrial tachycardia (OR, 0); number of people participating in the resus-
citation (OR, 2.5); and treatment with low-dose epinephrine (OR, 1.4), hydroxyethyl starch (OR, 0.5), naloxone (OR, 0.03), high-dose epinephrine (OR, 1.7), atropine (OR, 1,700), electrical defibrillation (OR, 1.7), abdominal compressions (OR, 0.28), dobutamine (OR, 0.003), or sodium bicarbonate (OR, 0.13; an OR > 1 indicates association with a positive outcome and an OR < 1 indicates an association with a negative outcome). As always with case series, only association can be documented, and it is possible there was no causal relationship between these various factors and ROSC. In addition to the recent RECOVER initiative,4 we hope that this information may prove useful when designing trials to determine whether a causal relationship actually exists between these factors and a successful outcome. Erik H. Hofmeister, DVM, DACVAA, MA Benjamin M. Brainard, VMD, DACVAA, DACVECC Department of Small Animal Medicine and Surgery College of Veterinary Medicine University of Georgia Athens, Ga Christine M Egger, DVM, MVSc, DACVAA College of Veterinary Medicine University of Tennessee Knoxville, Tenn Sangwook Kang, PhD Department of Statistics University of Connecticut Storrs, Conn 1.
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Hofmeister EH, Brainard BM, Egger CM, et al. Prognostic indicators for dogs and cats with cardiopulmonary arrest treated by cardiopulmonary cerebral resuscitation at a university teaching hospital. J Am Vet Med Assoc 2009;235:50–57. Fan J, Lv J. A selective overview of variable selection in high dimensional feature space. Statist Sinica 2010;20:101– 148. Yoon YJ, Park C, Hofmeister E, et al. Group variable selection in cardiopulmonary cerebral resuscitation data for veterinary patients. J App Stat 2012;39:1605–1621. Fletcher DJ, Boller M, Brainard BM, et al. RECOVER evidence and knowledge gap analysis on veterinary CPR. Part 7: clinical guidelines. J Vet Emerg Crit Care 2012;22(suppl 1):S102–S131.
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