Oo – this was a good month! Wish I had seen these papers when they came out – 40 great articles addressing lots of medical management of overdose, as well as overdose prevention programs.
Thanks again to Rebecca Martinez, Cathleen Beliveau, Nataliya Karashchuk, and Laila Esfandiari at the Center on Substance Use and Health (www.csuhsf.org) for collaborating to produce these summaries!
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1) A national survey of approaches to manage the ICU patient with opioid use disorder.
Reichheld AM, Hills-Evans K, Sheehan JK, Tocci NX, Tandon M, Hsu D, Marshall J, O’Donoghue S, Stevens JP.
J Crit Care. 2019 Jun 29;54:42-47. doi: 10.1016/j.jcrc.2019.06.032. [Epub ahead of print]
Comments: Managing patients with opioid use disorder can be complicated, more so when taking methadone for treatment, and even more so when taking buprenorphine due to the partial agonist effect of that drug. I love the word “iatrogenic”, which basically means “caused by the medical system”, and pertains frequently to what happens to patients on buprenorphine treatment when they are admitted to the hospital. Buprenorphine is often stopped when it shouldn’t be, patients are in agony for prolonged periods, and end up discharged on huge doses of full agonists, like hydromorphone (Dilaudid), and relapsing to illicit opioid use. It can be extremely disruptive.
Ashford RD, Brown AM, Dorney G, McConnell N, Kunzelman J, McDaniel J, Curtis B.
Addict Behav. 2019 Jun 26;98:106037. doi: 10.1016/j.addbeh.2019.106037. [Epub ahead of print]
Comments: Community-based participatory research is fascinating.
Ashford RD, Brown AM, McDaniel J, Neasbitt J, Sobora C, Riley R, Weinstein L, Laxton A, Kunzelman J, Kampman K, Curtis B.
Addict Behav. 2019 Jun 21;98:106031. doi: 10.1016/j.addbeh.2019.106031. [Epub ahead of print]
Comments: My university dropped Elsevier, so I can’t access this one and the abstract doesn’t give details on the model proposed, except that it involves using medications which is key to treating opioid use disorder.
4) Prescription opioid misuse among U.S. Hispanics.
Cano M.
Addict Behav. 2019 Jun 13;98:106021. doi: 10.1016/j.addbeh.2019.06.010. [Epub ahead of print]
Comments: The narrative surrounding the opioid epidemic has mostly focused on low-income white communities. However, just because the overall prevalence of opioid misuse among U.S. Hispanics is low doesn’t mean we can ignore this population. It turns out that the higher the generation of U.S. Hispanic adults, the higher the prevalence of prescription opioid misuse (e.g 6.8% prevalence 3rd generation and 6.2% for higher than 3rd generation Hispanics). English language orientation and length of time living in the U.S. were also associated with higher odds of past-year and lifetime prescription opioid misuse.
5) State Approaches to Addressing the Overdose Epidemic: Public Health Focus Needed.
Davis C, Green T, LaSalle L, Beletsky L.
J Law Med Ethics. 2019 Jun;47(2_suppl):43-46. doi: 10.1177/1073110519857315.
Comments: Overview of the common approaches used by states to address opioid-related harm, some of which are public health-based (i.e. overdose prevention and syringe exchange programs) while others are more punitive (i.e. drug-induced homicide statutes, compulsory treatment for OUD). Article stresses that public health approaches reduce opioid-related harm while punitive approaches exacerbate it by further stigmatizing drug use and discouraging people who use drugs from seeking care after an overdose.
6) Computational Systems Pharmacology-Target Mapping for Fentanyl-laced Cocaine Overdose.
Cheng J, Wang S, Lin W, Wu N, Wang Y, Chen M, Xie XS, Feng Z.
ACS Chem Neurosci. 2019 Jun 29. doi: 10.1021/acschemneuro.9b00109. [Epub ahead of print]
Comments: This paper tries to look at overdoses from fentanyl and cocaine (most believe that it is rarely “fentanyl-laced cocaine”, but instead generally co-use or mistaken use) by looking at genes, receptors, etc., that the drugs bind through simulations. It’s an interesting concept and one that is a bit over my head, admittedly. Unfortunately, the results and discussion are one section so it’s difficult to tease out the conclusions of the authors, besides that a cannabinoid 2 agonist should be used to treat cocaine and fentanyl overdose.
7) The Role of Pharmacists in Safe Opioid Dispensing.
Gregory T, Gregory L.
J Pharm Pract. 2019 Jun 30:897190019852803. doi: 10.1177/0897190019852803. [Epub ahead of print]
Comments: Review article that describes the role of pharmacists in the era of opioid pharmacovigilance. Mentions patient education about medications and naloxone, but focuses mostly on reduction of opioid diversion and use of non-prescription opioids through identification of “red-flag” behaviors. Missed opportunity for a discussion about the patient/pharmacist relationship as a way for patients to seek further education about their medications.
Haffajee RL, Lin LA, Bohnert ASB, Goldstick JE.
JAMA Netw Open. 2019 Jun 5;2(6):e196373. doi: 10.1001/jamanetworkopen.2019.6373.
Comments: In this cross-sectional study, “opioid high-risk counties” are defined by low availability of providers who can prescribe medications for OUD and high overdose mortality rate. Out of 3142 counties in the U.S., 419 were identified as opioid high-risk. Characteristics of these counties include higher rates of unemployment, micropolitan rather than metropolitan (e.g. <10,000 people), lower primary care provider density and located in East North Central, South Atlantic, or Mountain divisions.
Farrugia A.
Addiction. 2019 Jun 27. doi: 10.1111/add.14660. [Epub ahead of print] No abstract available.
Comments: Emergency medical responders can have stigmatizing attitudes and uncaring professional practices towards people they revive from overdose. Understandably, this increases the chance of conflictual encounters; however, providers are more likely to perceive these encounters as a sign of ingratitude rather than a byproduct of poor practices, thus generating a circular stigmatizing dynamic. This article posits that strategies such as addiction stigma reduction education initiatives and better naloxone administration practices are not sufficient to resolve the problem of stigma in healthcare. Accordingly, “more ambitious disruptions” to stigma must be undertaken, although what these disruptions might look like is not articulated.
10) Pain Management Strategies To Reduce Opioid Use Following Total Knee Arthroplasty.
Derogatis MJ, Sodhi N, Anis HK, Ehiorobo JO, Bhave A, Mont MA.
Surg Technol Int. 2019 Jun 25;35. pii: sti35/1156. [Epub ahead of print]
Comments: A review on the literature describing non-narcotic treatments to manage pain following total knee arthroplasty (TKA) finds conflicting evidence on prescribing acetaminophen or gabapentinoids and subsequent reduced opioid use. Multiple studies identified reductions in TKA pain with knee braces as a recommended non-invasive and non-pharmacological treatment. Full article unavailable.
Hsu HJ, Yang Y, Pavuluri V, Abraham C, Naraharisetti SB, Ashraf M, Al-Ghabeish M.
AAPS PharmSciTech. 2019 Jun 24;20(6):232. doi: 10.1208/s12249-019-1452-6.
Comments: The science of intranasal naloxone gets interesting when you try to ensure it will be absorbed – and you try to ensure it lasts a long time. Low pH helps it last longer but reduces absorption. Benzalkonium chloride improves absorption a lot, benzyl alcohol somewhat.
Essler JL, Smith PG, Berger D, Gregorio E, Pennington MR, McGuire A, Furton KG, Otto CM.
Animals (Basel). 2019 Jun 22;9(6). pii: E385. doi: 10.3390/ani9060385.
Comments: Dog’s olfactory abilities are not impacted or impaired by the administration of intranasal or intramuscular naloxone to reverse intravenous fentanyl sedation. However, the article starts out with the premise that exposure to fentanyl in first responders causes overdose. This is not true – unless they are pasting on fentanyl patches that have been designed to improve dermal absorption and then waiting 12 hours.
Sexton SM, Armstrong A, Gatton O, Rhodes LA, Marciniak MW.
J Am Pharm Assoc (2003). 2019 Jun 20. pii: S1544-3191(19)30144-X. doi: 10.1016/j.japh.2019.03.015. [Epub ahead of print]df
Comments: A community pharmacy utilized a standardized team-based approach for identifying naloxone-eligible patients, which resulted in a >300% increase in naloxone orders over the course of a year in comparison to the control store (which followed standard of practice). Full text not available.
14) One-Year Mortality of Patients After Emergency Department Treatment for Nonfatal Opioid Overdose.
Weiner SG, Baker O, Bernson D, Schuur JD.
Ann Emerg Med. 2019 Jun 19. pii: S0196-0644(19)30343-9. doi: 10.1016/j.annemergmed.2019.04.020. [Epub ahead of print]
Comments: Can’t access full article so may be missing something here. Paper addresses mortality following opioid overdose cared for in emergency departments in Massachusetts. About 6.5% died within one year, which is markedly high, but they don’t describe what people died from so their conclusion that substance use interventions are needed may or may not be correct based on the data. The statistics presented in the abstract, moreover, are a bit strange, as they devote lines to basically just giving the proportion of the proportions in previous sentences. Would be nice to see a more sophisticated analysis from such a fantastic dataset.
Sohn M, Talbert JC, Huang Z, Lofwall MR, Freeman PR.
JAMA Netw Open. 2019 Jun 5;2(6):e196215. doi: 10.1001/jamanetworkopen.2019.6215.
Comments: Suggests that naloxone coprescription laws are associated with increased dispensing of prescribed naloxone in pharmacies.
Southwell M, Shelly S, MacDonald V, Verster A, Maher L.
Curr Opin HIV AIDS. 2019 Jun 18. doi: 10.1097/COH.0000000000000566. [Epub ahead of print]
Comments: Harm reduction programs are still extremely underfunded and insufficiently supported, stigmatizing people who use drugs and creating barriers to care. New(ish) innovations discussed include peer distribution of naloxone, low dead space syringes, drug consumption rooms and drug-checking services.
Hazlehurst B, Green CA, Perrin NA, Brandes J, Carrell DS, Baer A, DeVeaugh-Geiss A, Coplan PM.
Pharmacoepidemiol Drug Saf. 2019 Jun 19. doi: 10.1002/pds.4810. [Epub ahead of print]
Comments: Electronic health records generally don’t include fields for substance use, such as whether or not someone injects drugs. These data may exist in provider notes, although patients know that those data in health records can stigmatize them, lead providers not to care for them (e.g. orthopedic surgeons), and cause financial and legal headaches (such as losing access to life insurance) – thus patients may understandably conceal drug use from their providers as much as possible and providers, particularly in this age of open medical records, may alter their language to allow patients that confidentiality while trying not to compromise patient care.
In the mix of this, “big data” and other efforts to use existing data sources has led a lot of substance use research toward electronic health records. This study attempted to create a natural language processing algorithm to identify opioid overdoses. It did fairly well but hit some snags, particularly in the validation cohort. Intentional overdose was readily identified. About two-thirds of unintentional overdoses were identified, with about 11% of the cases identified being false positives. Identifying specific substances got much more problematic. Overall, a much needed step toward understanding how to do this – but we still need to interact with actual people.
Wang JJ, Poirier V, Carvalho AM, Biary R, Su MK.
Travel Med Infect Dis. 2019 Jun 16. pii: S1477-8939(19)30100-0. doi: 10.1016/j.tmaid.2019.06.003. [Epub ahead of print] No abstract available.
Comments: Abstract and full text unavailable.
Oldfield BJ, Tetrault JM, Wilkins KM, Edelman EJ, Capurso NA.
Subst Abus. 2019 Jun 18:1-6. doi: 10.1080/08897077.2019.1621241. [Epub ahead of print]
Comments: Describes a mandatory educational intervention for medical students to provide overdose prevention information in a harm reduction framework, with a post-survey showing improved knowledge and attitudes.
20) Comprehensive Perioperative Management Considerations in Patients Taking Methadone.
Cornett EM, Kline RJ, Robichaux SL, Green JB, Anyama BC, Gennuso SA, Okereke EC, Kaye AD.
Curr Pain Headache Rep. 2019 Jun 17;23(7):49. doi: 10.1007/s11916-019-0783-z. Review.
Comments: Perioperative pain management strategies for patients on medications for opioid use disorder, including methadone, should be multimodal. Opioid-sparing techniques can be used when appropriate. Unable to access full article for more details through Elsevier.
Goldman JE, Krieger MS, Buxton JA, Lysyshyn M, Sherman SG, Green TC, Bernstein E, Hadland SE, Marshall BDL.
Subst Abus. 2019 Jun 17:1-8. doi: 10.1080/08897077.2019.1616245. [Epub ahead of print]
Comments: In a small study of 93 participants who use drugs, those who had experienced a suspected fentanyl-related overdose (n=18) were more likely to carry and administer naloxone. This same group was more likely to have administered naloxone to someone else experiencing an overdose than those who had never overdosed or who had overdosed on substances not believed to be fentanyl.
Gushgari AJ, Venkatesan AK, Chen J, Steele JC, Halden RU.
Water Res. 2019 Jun 3;161:171-180. doi: 10.1016/j.watres.2019.06.003. [Epub ahead of print]
Comments: Analyzing municipal raw wastewater from two Midwestern cities for morphine, codeine, oxycodone, heroin, fentanyl, and some opioid metabolites to try to predict the number of opioid overdose deaths. Can’t access the full article so difficult to verify, but they claim to have been able to use the algorithm to fairly accurately predict the number of deaths in 2016.
23) Naloxone interventions in opioid overdoses: a systematic review protocol.
Shaw LV, Moe J, Purssell R, Buxton JA, Godwin J, Doyle-Waters MM, Brasher PMA, Hau JP, Curran J, Hohl CM.
Syst Rev. 2019 Jun 11;8(1):138. doi: 10.1186/s13643-019-1048-y.
Comments: Protocol paper for a systematic review of administration of naloxone for opioid overdose (looking at dosing, effectiveness, and adverse effects of naloxone). Not an urgent study, as naloxone is known to be safe in a wide range of doses. However, administering naloxone to an individual experiencing an overdose often causes immediate opioid withdrawal and significant discomfort in that individual. Additional research on naloxone dose administered for different opioids, especially suspected ultra-potent opioids like fentanyl, could be a useful tool in understanding how to humanely reverse opioid overdoses.
24) Pulmonary Complications of Opioid Overdose Treated With Naloxone.
Farkas A, Lynch MJ, Westover R, Giles J, Siripong N, Nalatwad A, Pizon AF, Martin-Gill C.
Ann Emerg Med. 2019 Jun 7. pii: S0196-0644(19)30309-9. doi: 10.1016/j.annemergmed.2019.04.006. [Epub ahead of print]
Comments: Unable to access full article. This retrospective, observational, cross-sectional study found that patients who had received more than 4.4mg of naloxone (in other words more than 1 dose) were 62% more likely to have a pulmonary complication like aspiration pneumonia. This is not remotely unexpected, as multiple doses are administered when someone is not responding and thus has further pulmonary compromise from their overdose.
25) [Improve the benefit/risk balance of methadone by respecting its pharmacological specificities].
Frauger E, Fouilhé Sam-Laï N, Mallaret M, Micallef J; le French Addictovigilance Network (FAN).
Therapie. 2019 Jun;74(3):383-388. doi: 10.1016/j.therap.2018.09.070. Epub 2018 Sep 27. French.
Comments: French article, full-text unavailable, describes methadone-related adverse events (overdose, diversion, death) from 2003-2017 in France.
26) Opioid use and misuse: health impact, prevalence, correlates and interventions.
Bolshakova M, Bluthenthal R, Sussman S.
Psychol Health. 2019 Jun 8:1-35. doi: 10.1080/08870446.2019.1622013. [Epub ahead of print]
Comments: A broad review and history of opioid use and misuse in recent years examining individual and environmental factors that lead to problematic use, preventative strategies, and current alternatives to pain management. This article calls for a balance of limiting access to opioids for potential misusers and ensuring that patients who need pain management do not experience additional barriers to accessing prescription opioids. However, the question remains about how this distinction could be implemented in an unbiased way.
27) Development of vaccines to treat opioid use disorders and reduce incidence of overdose.
Pravetoni M, Comer SD.
Neuropharmacology. 2019 Jun 4:107662. doi: 10.1016/j.neuropharm.2019.06.001. [Epub ahead of print] Review.
Comments: Review article; discusses possibilities of using vaccines to treat substance use disorders, and opioid use disorders in particular. As discussed in our last release, there are both logistic (there is such a variety of opioids and the market is shifting constantly) and potential ethical issues with vaccines, particularly related to forced use in criminal justice settings and particularly relevant to opioid use disorder, for which we already have effective treatments. Unable to access full article through Elsevier.
Brett J, Wylie CE, Raubenheimer J, Isbister GK, Buckley NA.
Br J Clin Pharmacol. 2019 Jun 7. doi: 10.1111/bcp.14019. [Epub ahead of print]
Comments: Interesting article. Can’t access the full text to really evaluate what they did. Seems they combined mortality data with dispensing data and data from the Hunter Area Toxicology Service (in Australia; seems to be an emergency department of sorts) to generate two data points: 1) the fatal toxicity index (FTI) = the number of fatal poisonings from a drug per year of daily dispensed drug; and (2) case fatality (CF) = the rate of fatal poisonings to total poisonings. There were 444 overdose deaths and 21,296 overdoses recorded from 2002 to 2016. Of prescribed drugs, opioids had the highest FTI (40.3 deaths per 100 years of dispensed drug) and CF (12.4% of overdoses resulted in death). Among the opioids, the highest FTI came from fentanyl, methadone and morphine (does Australia have illictly-manufactured fentanyl? That would mess up this analysis). Heroin had a CF of 26.4%. This is interesting, because heroin overdose is well established to result in death in about 4% of cases; these data suggest that, among heroin overdoses that make it to an emergency department (or toxicology unit?), 26.4% result in death. These results are quite useful for modeling on overdose prevention.
29) Availability and Cost of Naloxone Nasal Spray at Pharmacies in Philadelphia, Pennsylvania, 2017.
Guadamuz JS, Alexander GC, Chaudhri T, Trotzky-Sirr R, Qato DM.
JAMA Netw Open. 2019 Jun 5;2(6):e195388. doi: 10.1001/jamanetworkopen.2019.5388.
Comments: Evaluation of naloxone nasal spray availability at Philadelphia pharmacies following a standing order allowing pharmacies to dispense naloxone without a prescription. Findings show that only 34% of pharmacies had naloxone in stock and it was less likely to be available in areas with higher rates of opioid overdose deaths. Average out of pocket cost was $145. Results indicate that naloxone access is still restricted, especially for communities that may need it most.
Winograd RP, Werner KB, Green L, Phillips S, Armbruster J, Paul R.
Subst Abus. 2019 Jun 6:1-7. doi: 10.1080/08897077.2019.1616348. [Epub ahead of print]
Comments: This study examined a way to classify concerns about naloxone distribution on a risk compensation belief scale and found that amongst service providers including police, EMS, social services and others, attending an overdose education and naloxone distribution training decreased beliefs about naloxone-related risk compensation behaviors. Education among service providers is important to reduce stigma surrounding naloxone distribution.
Park JN, Sherman SG, Rouhani S, Morales KB, McKenzie M, Allen ST, Marshall BDL, Green TC.
J Urban Health. 2019 Jun;96(3):353-366. doi: 10.1007/s11524-019-00365-1.
Comments: Study investigating trends in willingness to use safe consumption spaces among people who use drugs in the (north)east. 77% of 326 opioid users from three major cities were willing to use a safe consumption space. Female gender, racial minority status, and injecting in public spaces were associated with higher willingness to use a safe consumption space.
32) Prevention of Opioid Overdose.
Babu KM, Brent J, Juurlink DN.
N Engl J Med. 2019 Jun 6;380(23):2246-2255. doi: 10.1056/NEJMra1807054. Review. No abstract available.
Comments: Review of provider strategies for prevention of opioid overdose among patients who are initiating opioid therapy, those on long-term opioid therapy and those living with an opioid use disorder. Strategies include tapering, medication-assisted treatment, use of buprenorphine for pain management, naloxone provision, etc.
Irvine MA, Kuo M, Buxton JA, Balshaw R, Otterstatter M, Macdougall L, Milloy MJ, Bharmal A, Henry B, Tyndall M, Coombs D, Gilbert M.
Addiction. 2019 Jun 5. doi: 10.1111/add.14664. [Epub ahead of print]
Comments: Mathematical model based on British Columbia data evaluating effect of opioid overdose interventions. Take-home naloxone averted the highest number of deaths (1580 over four years), which is in line with previous studies showing the effectiveness of providing take-home naloxone. They further estimated that 230 deaths were prevented by safe consumption services and 590 by medications for opioid use disorder treatment. This occurred during a tragic opioid overdose death crisis in the region, thus authors note that the number of overdose deaths did not decline in the context of expanded overdose prevention services.
Kim HK, Connors NJ, Mazer-Amirshahi ME.
Expert Opin Drug Saf. 2019 Jun;18(6):465-475. doi: 10.1080/14740338.2019.1613372. Epub 2019 May 16. Review.
Comments: Fentanyl and its analogs are coming (or already came) to dominate the street opioid supply in North America. There is concern that higher or repeated doses of naloxone may be required to reverse fentanyl. When administered in clinical settings, fentanyl is just as responsive to naloxone as other opioids. In the community, however, people may consume a substantial overdose of fentanyl which, because naloxone is a competitive antagonist, may require additional naloxone. Further, and this may be a common cause of the perceived need, fentanyl overdoses occur rapidly and can progress to cardiac arrest much more quickly than heroin overdoses. Many of the cases of fentanyl overdose are “worse” – by which I mean further along, more severe, and more likely to also involve the heart stopping – than what we are used to seeing with heroin or other opioids.
Latkin CA, Gicquelais RE, Clyde C, Dayton L, Davey-Rothwell M, German D, Falade-Nwulia S, Saleem H, Fingerhood M, Tobin K.
Int J Drug Policy. 2019 Jun;68:86-92. doi: 10.1016/j.drugpo.2019.03.012. Epub 2019 Apr 23.
Comments: Experiencing stigma was associated with likelihood of experiencing a non-fatal overdose, as was using drugs in a public setting. Data on these subjects and overdose risk has been mixed over the years. Unable to access full article through Elsevier.
36) U.S. National 90-Day Readmissions After Opioid Overdose Discharge.
Peterson C, Liu Y, Xu L, Nataraj N, Zhang K, Mikosz CA.
Am J Prev Med. 2019 Jun;56(6):875-881. doi: 10.1016/j.amepre.2018.12.003. Epub 2019 Apr 17.
Comments: Out of 58,850 admissions for opioid overdose in the US in 2016, 24% resulted in a readmission within 90 days; 3% (1,658) were readmitted for another overdose. Leaving against medical advice was associated with readmission (no surprise for those of us who provide inpatient care), suggesting the real benefit that addiction medicine consult services could provide.
Sherman SG, Morales KB, Park JN, McKenzie M, Marshall BDL, Green TC.
Int J Drug Policy. 2019 Jun;68:46-53. doi: 10.1016/j.drugpo.2019.03.003. Epub 2019 Apr 13.
Comments: 63% of this cohort of street-based people who use drugs had overdosed; 42% had witnessed a fatal overdose. 90% thought checking drugs with things like fentanyl strips would help then prevent overdose. Older and non-white participants were more likely to intend to use drug checking.
38) Opioid-prescribing Patterns for Pediatric Patients in the United States.
Groenewald CB.
Clin J Pain. 2019 Jun;35(6):515-520. doi: 10.1097/AJP.0000000000000707.
Comments: Narrative review noting the increasing prescribing of opioids to children since 2000 (I assume that trend has reversed in recent years, but don’t know the data). 40% of children receive opioids during hospitalization. By the age of 18, almost 20% of children in the United States report having received an opioid prescription at some point in their lifetime.
Stopka TJ, Amaravadi H, Kaplan AR, Hoh R, Bernson D, Chui KKH, Land T, Walley AY, LaRochelle MR, Rose AJ.
Int J Drug Policy. 2019 Jun;68:37-45. doi: 10.1016/j.drugpo.2019.03.024. Epub 2019 Apr 11.
Comments: Fascinating analysis in Massachusetts looking to see if clusters of potentially inappropriate opioid prescribing were associated with clusters of opioid overdoses from 2011 to 2016. They found that prescribing didn’t entirely explain overdoses. Not surprising, but useful for prioritizing prevention resources.
Heaton JD, Bhandari B, Faryar KA, Huecker MR.
J Emerg Med. 2019 Jun;56(6):642-651. doi: 10.1016/j.jemermed.2019.02.015. Epub 2019 Apr 5.
Comments: This study makes the case for standardizing the emergency department observation period for patients who receive naloxone after a heroin overdose. They felt a need to provide oxygen or naloxone to 4.6% of patients after two hours of observation, 1.9% after 3 hours, and 0.9% after 4 hours.